Design of peptides: synthesis, crystal structure, molecular conformation, and conformational calculations of N-Boc-L-Phe-Dehydro-Ala-OCH3.

It is noteworthy that the dehydro-Ala residue adopts an extended conformation that is different than those observed in dehydro-Phe, dehydro-Leu, and dehydro-Abu. The peptide N-Boc-L-Phe-dehydro-Ala-OCH3 (C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N-Boc-L-Phe-L-Ser-OCH3 to N-Boc-L-Phe-dehydro-Ala- OCH3. It was crystallized from its solution in a methanol-water mixture at room temperature. The crystals belong to the monoclonic space group P2(1), with a = 9.577(1) A, b = 5.195(3) A, c = 19.563(3) A, beta = 94.67(5) degrees, V = 970.1(6) A3, Z = 2, dm = 1.201(5) Mg m-3, dc = 1.197(5) Mg m-3. The structure was determined using direct method procedures. It was refined by a full-matrix least-squares procedure to an R value of 0.048 for 1370 observed reflections. The C2 alpha-C2 beta distance is 1.327(8) A, while the bond angles N2-C2 alpha-C2' and C1'-N2-C2 alpha are 109.8(5) degrees and 127.8(5) degrees, respectively. The backbone adopts a nonspecific conformation with dehydro-Ala in a fully extended conformation with the following torsion angles: theta 1 = 175.2(4) degrees, omega 0 = 170.2(4) degrees, phi 1 = 135.8(5) degrees, psi 1 = -22.6(6) degrees, omega 1 = 168.5(5) degrees, phi 2 = -170.3(5) degrees, psi 2T = -178.6(5) degrees, theta T = 178.4(7) degrees. The rigid planar and trans conformation of dehydro-Ala forces Phe to adopt a strained conformation. The Boc group has a trans-trans conformation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis, crystal structure, and molecular conformation of peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH

The peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH was synthesized by the usual workup procedure and finally coupling the N-Boc-L-Pro-dehydro-Phe to glycine. The peptide crystallizes in monoclinic space group P2(1) with a = 8.951(4) A, b = 5.677(6) A, c = 21.192(11) A, beta = 96.97(4) degrees, V = 1069(1) A3, Z = 2, dm = 1.295(5) Mgm-3, and dc = 1.297(4) Mgm-3. The structure was determined by direct methods using SHELXS86. The structure was refined by the block-diagonal least-squares procedure to an R value of 0.074 for 1002 observed reflections. The C alpha 2-C beta 2 distance of 1.33(2) A is an appropriate double bond length. The angle C alpha 2-C beta 2-C gamma 2 is 133(1) degrees. The peptide backbone torsion angles are theta 1 = -167(1) degrees, omega 0 = 179(1) degrees, phi 1 = -48(1) degrees, psi 1 = 137(1) degrees, omega 1 = 175(1) degrees, phi 2 = 65(2) degrees, psi 2 = 15(2) degrees, omega 2 = -179(1) degrees, and phi 3 = -166(1) degrees. These values show that the Boc group has a trans-trans conformation while the peptide backbone adopts a beta-turn II conformation, which is stabilized by an intramolecular hydrogen bond of length of 3.05(1) A. The structures of dehydro-Phe containing peptides suggest that the dehydro-Phe promotes the beta-turn II conformation. The five-membered pyrrolidine ring of the Pro residue adopts an ideal C gamma-exo conformation with torsion angles chi 1(1) = -24(1) degrees, chi 2(1) = 34(1) degrees, chi 3(1) = -30(1) degrees, chi 4(1) = 15(1) degrees, and theta 0(1) = 6(1) degrees. The side-chain torsion angles in dehydro-Phe are chi 1(2) = -1(2) degrees, chi 2,1(2) = -176(1) degrees, and chi 2,2(2) = 8(2) degrees. The plane of C alpha 2-C beta 2-C gamma 2 is rotated with respect to the plane of the phenyl ring at 7(1) degrees, which indicates that the atoms of the side chain of dehydro-Phe are essentially coplanar. The molecules form a 2(1) screw axis related hydrogen-bonded rows along the b axis.     

Synthesis, crystal structure, and molecular conformation of N-Boc-L-Phe-dehydro-Leu-L-Val-OCH3

The peptide N-Boc-L-Phe-dehydro-Leu-L-Val-OCH3 was synthesized by the usual workup procedure and finally by coupling the N-Boc-L-Phe-dehydro-Leu-OH to valine methyl ester. It was crystallized from its solution in methanol-water mixture at 4 degrees C. The crystals belong to the triclinic space group P1 with a = 5.972(5) A, b = 9.455(6) A, c = 13.101(6) A, alpha = 103.00(4) degrees, beta = 97.14(5) degrees, gamma = 102.86(5) degrees, V = 690.8(8) A, Z = 1, dm = 1.179(5) Mg m-3 and dc = 1.177(5) Mg m-3. The structure was determined by direct methods using SHELXS86. It was refined by block-diagonal least-squares procedure to an R value of 0.060 for 1674 observed reflections. The C alpha 2-C beta 2 distance of 1.323(9) A in dehydro-Leu is an appropriate double bond length. The bond angle C alpha-C beta-C gamma in the dehydro-Leu residue is 129.4(8) degrees. The peptide backbone torsion angles are theta 1 = -168.6(6) degrees, omega 0 = 170.0(6) degrees, phi 1 = -44.5(9) degrees, psi 1 = 134.5(6) degrees, omega 1 = 177.3(6) degrees, phi 2 = 54.5(9) degrees, psi 2 = 31.1(10) degrees, omega 2 = 171.7(6) degrees, phi 3 = 51.9(8) degrees, psi T3 = 139.0(6) degrees, theta T = -175.7(6) degrees. These values show that the backbone adopts a beta-turn II conformation. As a result of beta-turn, an intramolecular hydrogen bond is formed between the oxygen of the ith residue and NH of the (i + 3)th residue at a distance of 3.134(6) A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis, crystal structure and molecular conformation of N-Ac-dehydro-Phe-L-Val-OH.

The peptide N-Ac-dehydro-Phe-L-Val-OH (C16H20N2O4) was synthesized by the usual workup procedure. The peptide crystallizes from its solution in acetonitrile at 4 degrees in hexagonal space group P6(5) with a = b = 11.874(2)A, c = 21.856(9) A, V = 2668(1) A3, Z = 6, dm = 1.151(3) g cm-3, dc = 1.136(4) g cm-3, CuK alpha = 1.5418 A, mu = 0.641 mm-1, F(000) = 972, T = 293 K. The structure was solved by direct methods and refined by least-squares procedure to an R value of 0.074 for 1922 observed reflections. In the dehydro-residue, the C1 alpha-C1 beta distance is 1.35(1) A while the bond angle C1 alpha-C1 beta-C1 gamma is 131.2(9) degrees. The backbone torsion angles are: omega 0 = 172(1) degrees, phi 1 = -60(2) degrees, psi 1 = -31(2) degrees, omega 1 = -179(1) degrees, phi 2 = 59(2) degrees. These values suggest that the peptide tends to adopt an alternating right-handed and left-handed helical conformation. The side chain torsion angles are: chi 1(1) = -6(2) degrees, chi 1(2.1) = -1(2) degrees, chi 1(2.2) = -178(2) degrees, chi 2(1.1) = 63(2) degrees and chi 2(1.2) = -173(1) degrees. These values show that the side chain of dehydro-Phe is planar whereas the valyl side chain adopts a sterically most preferred conformation. The molecules, linked by intermolecular hydrogen bonds and van der Waals forces, are arranged in helices along the c-axis. The helices are held side-by-side by van der Waals contacts.     

Crystal structure and molecular conformation of the peptide N-Boc-L-Gly-dehydro-Phe-NHCH3

The peptide N-Boc-L-Gly-dehydro-Phe-NHCH3 was synthesized by the combination of N-Boc-L-Gly-dehydro-Phe azlactone and methylamine. The peptide crystallizes in orthorhombic space group P2(1)2(1)2(1) with a = 5.679(2) A, b = 16.423(9) A, c = 19.198(10) A, V = 1791(2) A3, Z = 4, dm = 1.212(5) Mg m-3, dc = 1.237(1) Mg m-3. The structure was determined by direct methods using SHELXS 86. The structure was refined by full-matrix least squares procedure to an R value of 0.049 for 1509 observed reflections. The molecular dimensions are, in general, in good agreement with the standard values. The bond angle C alpha-C beta-C gamma in the dehydro-Phe residue is 133.6(5) degrees. The peptide backbone torsion angles are theta 1 = -171.4(4) degrees, omega 0 = 178.2(4) degrees, phi 1 = -57.2(6) degrees, psi 1 = 141.2(4) degrees, omega 1 = -174.4(4) degrees, phi 2 = 71.5(6) degrees, psi 2 = 7.2(6) degrees, and omega 2 = -179.8(5) degrees. These values show that the backbone adopts the beta-bend type II conformation. The Boc group has a trans-trans conformation. The side-chain torsion angles in dehydro-Phe are chi 2 = 1.6(9) degrees, chi 2(2, 1) = 0.5(9) degrees, and chi 2(2, 2) = 179.8(6) degrees. The plane of C2 alpha-C2 beta-C2 gamma is rotated with respect to the plane of the phenyl ring at 0.5(6) degrees, which indicates that the atoms of the side chain of the dehydro-Phe residue are essentially coplanar.(ABSTRACT TRUNCATED AT 250 WORDS)     

A sequence preference for nucleation of alpha-helix--crystal structure of Gly-L-Ala-L-Val and Gly-L-Ala-L-Leu: some comments on the geometry of leucine zippers

The synthetic peptide Gly-L-Ala-L-Val (C10H19N3O4.3H2O; GAV) crystallizes in the monoclinic space group P21, with a = 8.052(2), b = 6.032(2), c = 15.779(7) A, beta = 98.520(1) degree, V = 757.8 A3, Dx = 1.312 g cm-3, and Z = 2. The peptide Gly-L-Ala-L-Leu (C11H21N3O4.3H2O; GAL) crystallizes in the orthorhombic space group P212121, with a = 6.024(1), b = 8.171(1), c = 32.791(1) A, V = 1614 A3, Dx = 1.289 g cm-3, and Z = 4. Their crystal structures were solved by direct methods using the program SHELXS-86, and refined to an R index of 0.05 for 1489 reflections for GAV and to an R index of 0.05 for 1563 reflections for GAL. The tripeptides exist as a zwitterion in the crystal and assume a near alpha-helical backbone conformation with the following torsion angles: psi 1 = -150.7 degrees; phi 2, psi 2 = -68.7 degrees, -38.1 degrees; phi 3, psi 32 = -74.8 degrees, -44.9 degrees, 135.9 degrees for GAV; psi 1 = -150.3 degrees; phi 2, psi 2 = -67.7 degrees, -38.9 degrees; phi 3, psi 31, psi 32 = -72.2 degrees, -45.3 degrees, 137.5 degrees for GAL. Both the peptide units in both of the tripeptides show significant deviation from planarity [omega 1 = -171.3(6) degrees and omega 2 = -172.0(6) degrees for GAV; omega 1 = -171.9(5) degrees and omega 2 = -173.2(6) degrees for GAL]. The side-chain conformational angles chi 21 and chi 22 are -61.7(5) degrees and 175.7(5) degrees, respectively, for valine, and the side-chain conformations chi 12 and chi 23's are -68.5(5) degrees and (-78.4(6) degrees, 159.10(5) degrees) respectively, for leucine. Each of the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH3+ and COO- groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an alpha-helix.     

Crystal structure of tert.-butyloxycarbonyl-L-prolyl-D-alanyl-D-alanyl-N-methylamide. Dimeric beta-sheet formation.

The crystal structure of the tripeptide t-Boc-L-Pro-D-Ala-D-Ala-NHCH3, monohydrate, (C17H30N4O5.H2O, molecular weight = 404.44) has been determined by single crystal X-ray diffraction. The crystals are monoclinic, space group P2(1), a = 9.2585(4), b = 9.3541(5), c = 12.4529(4)A, beta = 96.449(3) degrees, Z = 2. The peptide units are in the trans and the tBoc-Pro bond in the cis orientation. The first and third peptide units show significant deviations from planarity (delta omega = 5.2 degrees and delta omega = 3.7 degrees, respectively). The backbone torsion angles are: phi 1 = -60 degrees, psi 1 = 143.3 degrees, omega 1 = -174.8 degrees, phi 2 = 148.4 degrees, psi 2 = -143.1 degrees, omega 2 = -179.7 degrees, phi 3 = 151.4 degrees, psi 3 = -151.9 degrees, omega 3 = -176.3 degrees. The pyrrolidine ring of the proline residue adopts the C2-C gamma conformation. The molecular packing gives rise to an antiparallel beta-sheet structure formed of dimeric repeating units of the peptide. The surface of the dimeric beta-sheet is hydrophobic. Water molecules are found systematically at the edges of the sheets interacting with the urethane oxygen and terminal amino groups. Surface catalysis of an L-Ala to D-Ala epimerization process by water molecules adsorbed on to an incipient beta-sheet is suggested as a mechanism whereby crystals of the title peptide were obtained from a solution of tBoc-Pro-D-Ala-Ala-NHCH3.     

Peptide crystal growth via vapor diffusion. Crystal structure of glycyl-L-tyrosyl-L-alanine dihydrate.

The structure of a dihydrated form of glycyl-L-tyrosyl-L-alanine (GYA) has been determined as part of a series of peptide structural investigations and development of microscale vapor diffusion experiments for peptide crystal growth. Crystals were grown by the hanging-drop method against sodium acetate. The tripeptide is a zwitterion in the crystal, adopting an extended conformation through glycine, a nearly perpendicular bend at tyrosine and a reverse turn for the C-terminal carboxylate. Principal backbone torsion angles are psi 1 175(1) degrees, omega 2 173(1) degrees, phi 2 -119(1) degrees, psi 2 120(1) degrees, omega 3 172(1) degrees, phi 3 -73(1) degrees, psi 31 -9(1) degrees, psi 32 171(1) degrees. The tyrosyl side chain adopts an unusual orientation (chi 1/2 = -86(1) degrees). The relationship of the GYA.2H2O structure to GYA sequences in proteins is examined, particularly as regards its helix-forming potential. Crystal data: C14H19N3O4.2H2O, M(r) = 345.36, orthorhombic, P2(1)2(1)2(1), a = 4.810 (4), b = 11.400(7), c = 30.162(23)A, V = 1653.8(24)A-3, Z = 4, Dx = 1.387 Mgm-3, lambda(CuK- alpha) = 1.540 A, mu = 9.053 mm-1, F(000) = 736, T = 199 K, R = 0.041 for 1458 observations with I greater than or equal to 3 sigma(I).     

Structure and conformation of linear peptides. VIII. Structure of t-Boc-glycyl-L-phenylalanine

The crystal structure of t-Boc-glycyl-L-phenylalanine (C14H22N2O5, molecular weight = 298) has been determined. Crystals are monoclinic, space group P2(1), with a = 7.599(1) A, b = 9.576(2), c = 12.841(2), beta = 97.21(1) degrees, Z = 2, Dm = 1.149, Dc = 1.168 g X cm-3. Trial structure was obtained by direct methods and refined to a final R-index of 0.064 for 1465 reflections with I greater than 1 sigma. The peptide unit is trans planar and is nearly perpendicular to the plane containing the urethane moiety. The plane of the carboxyl group makes a dihedral angle of 16.0 degrees with the peptide unit. The backbone torsion angles are omega 0 = -176.9 degrees, phi 1 = -88.0 degrees, psi 1 = -14.5 degrees, omega 1 = 176.4 degrees, phi 2 = -164.7 degrees and psi 2 = 170.3 degrees. The phenylalanine side chain conformation is represented by the torsion angles chi 1 = 52.0 degrees, chi 2 = 85.8 degrees.     

Structure and conformation of linear peptides. XIII. Structure of L-phenylalanyl-glycyl-glycine

The crystal structure of a tripeptide, L-phenylalanyl-glycyl-glycine (C13H17N3O4), molecular weight = 279.3, has been determined. The crystals are orthorhombic, space group P2(1)2(1)2(1), with a = 5.462(1) A, b = 15.285(5), c = 16.056(4), Z = 4, and P (calc) = 1.384 g.cm-3. The final R-index is 0.052 for 866 reflections with sin theta/lambda less than or equal to 0.55 A-1 and I greater than 1 sigma. The molecule exists as a zwitterion, with the N-terminus protonated and the C-terminus in an ionized form. Both the peptide units are in the trans configuration and planar, though one of them shows significant deviations from planarity ([delta w[ = 5.1 degrees). The peptide backbone is folded, with the torsion angles of: psi 1 = 116.2(5) degrees, omega 1 = 178.8(4), phi 2 = -89.7(5). psi 2 = -28.9(6), omega 2 = -174.9(4), phi 3 = 134.9(5), psi 31 = 7.8(6), psi 32 = -172.6(4). The terminal glycine adopts a "D-residue" conformation. For the sidechain of phenylalanine, chi 1 = 175.5(4), chi 2 = -127.0(6).     

Crystal structure and conformation of L-pyroglutamyl-L-alanine

Crystals of the dipeptide, pyroglutamyl-alanine (C8H12N2O4) grown from aqueous methanol are monoclinic, space group P2(1) with the following cell parameters: a = 4.863(2), b = 16.069(1), c = 6.534(2)A and beta = 109.9(2) degrees, V = 480.0A3, Mr = 200.2, Dc = 1.385 g cm-3, and Z = 2. The crystal structure was solved by the application of direct methods and refined to an R value of 0.044 for 699 reflections with I greater than 2 sigma. The amide of the pyroglutamyl side chain is cis, omega 1 = 2.6(7) degrees; the peptide unit is trans and appreciably non-planar (omega 2 = 167.4(5) degrees). The backbone torsional angles are: psi 1 = 166.1(5), phi 2 = -90.3(6), and psi 2 = -22.4(6) degrees. This structure contains a short (2.551(5)A) intermolecular hydrogen bond between the carboxyl OH and the N-acyl oxygen, a feature common to most acyl amino acids and acyl peptides.     

Structure and conformation of linear peptides. XII. Structure of tryptophanyl-glycyl-glycine dihydrate

The crystal structure of a tripeptide, tryptophanyl-glycyl-glycine dihydrate (C15H18N4O4.2H2O, molecular weight = 354) has been determined. The crystals are orthorhombic, space group P2(1)2(1)2(1), with a = 7.875 (1) A, b = 9.009(1), c = 24.307(1) and Z = 4. The final R-index is 0.058 for 1488 reflections [sin theta)/lambda less than or equal to 0.6 A-1) with I greater than 2 sigma (I). The molecule exists as a zwitterion, with terminal NH3+ and COO- groups. The peptide units are trans and nearly perpendicular to the plane of the carboxyl group. The backbone torsion angles are: psi 1 = 132.7 degrees, omega 1 = 174.2 degrees, phi 2 = 88.2 degrees, psi 2 = 8.6 degrees, omega 2 = -179.8 degrees, phi 3 = -85.2 degrees, psi 31 = -178.1 degrees, psi 32 = 5.0 degrees. For the sidechain of tryptophan, chi 1 = -171.6 degrees, chi 2 = 101.0 degrees.     

Crystal structure and conformation of glycyl-glycyl-sarcosine

Crystals of the tripeptide, glycyl-glycyl-sarcosine (C7H13N3O4) from aqueous methanol are orthorhombic, space group Pbcn with cell parameters at 294 K of a = 8.279(1), b = 9.229(4), c = 24.447(5)A, V = 1868.0 A3, M.W. = 203.2, and Z = 8. The crystal structure was solved and refined using CAD-4 data (1171 reflections greater than or equal to 3 sigma) to a final R-value of 0.053. The first peptide linkage is trans and planar whereas the second peptide link between Gly and sarcosine is cis and appreciably non-planar (w = 7.4 degrees). The peptide backbone has an extended conformation at the N-terminal part but adopts a polyglycine-II type of conformation at the C-terminal part. The backbone torsion angles are: psi 1 = -173.9, w1 = -177.8, (phi 2, psi 2) = (-178.8, -170.8), w2 = 7.4, (phi 3, psi 3) = (-81.6, 165.6 degrees).     

Conformation of a cyclic decapeptide analog of a repeat pentapeptide sequence of elastin: cyclo-bis(valyl-prolyl-alanyl-valyl-glycyl)

The conformation of a cyclic decapeptide analog of a repeat sequence of elastin has been determined in the crystalline state using X-ray crystallographic techniques. Tetragonal crystals were grown from a solution of the decapeptide in water; space group P4(2)2(1)2, a = 19.439(2) & c = 13.602(1) A, with four formula units (C40H66N10O10.4H2O) per unit cell. The cyclic decapeptide in the crystal exhibits exact twofold symmetry. The asymmetric unit contains one pentapeptide and two water molecules for a total of 32 nonhydrogen atoms. The structure has been determined by the application of direct methods and refined by full-matrix least squares to an R index of 0.053 for 2272 reflections with intensities greater than 2 sigma(I). The backbone conformation of the asymmetric pentapeptide can be described as consisting of a double beta bend of Type III-I. The Type III turn has Pro (phi = -59.3 degrees, psi = -26.8 degrees) and Ala (phi = -65.9 degrees, psi = -23.1 degrees) at the corners while Type I turn has Ala (phi = -65.9 degrees, psi = -23.1 degrees) and Val (phi = -98.9 degrees, psi = 8.3 degrees) as the corner residues. The cyclic decapeptide has two such double bends linked together by Gly-Val bridges.     

Significant conformational changes in an antigenic carbohydrate epitope upon binding to a monoclonal antibody.

Transferred nuclear Overhauser enhancement spectroscopy (TRNOE) was used to observe changes in a ligand's conformation upon binding to its specific antibody. The ligands studied were methyl O-beta-D-galactopyranosyl(1----6)-4-deoxy-4-fluoro-beta-D-galactopyra nos ide (me4FGal2) and its selectively deuteriated analogue, methyl O-beta-D-galactopyranosyl(1----6)-4-deoxy-2-deuterio-4-fluoro-beta -D- galactopyranoside (me4F2dGal2). The monoclonal antibody was mouse IgA X24. The solution conformation of the free ligand me4F2dGal2 was inferred from measurements of vicinal 1H-1H coupling constants, long-range 1H-13C coupling constants, and NOE cross-peak intensities. For free ligand, both galactosyl residues adopt a regular chair conformation, but the NMR spectra are incompatible with a single unique conformation of the glycosidic linkage. Analysis of 1H-1H and 1H-13C constants indicates that the major conformer has an extended conformation: phi = -120 degrees; psi = 180 degrees; and omega = 75 degrees. TRNOE measurements on me4FGal2 and me4F2dGal2 in the presence of the specific antibody indicate that the pyranose ring pucker of each galactose ring remains unchanged, but rotations about the glycosidic linkage occur upon binding to X24. Computer calculations indicate that there are two sets of torsion angles that satisfy the observed NMR constraints, namely, phi = -152 +/- 9 degrees; psi = -128 +/- 7 degrees; and omega = -158 +/- 6 degrees; and a conformer with phi = -53 +/- 6 degrees; psi = 154 +/- 10 degrees; and omega = -173 +/- 6 degrees. Neither conformation is similar to any of the observed conformations of the free disaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Crystal-state structural analysis of two gamma-lactam-restricted analogs of Pro-Leu-Gly-NH2

The crystal structures of two analogs of Pro-Leu-Gly-NH2 (1), containing a gamma-lactam conformational constraint in place of the -Leu-Gly- sequences, are described. The highly biologically active (S,R)-diastereomer 2a is semi-extended at the C-terminus, with the N-terminal Pro residue in the unusual "C5" conformation [psi 1 = -0.8(15) degrees] stabilized by a (peptide)N-H...N(amino) intramolecular H-bond [the N(3)...N(4) separation is 2.687(11)A]. Conversely, the N,N'-isopropylidene aminal trihydrate of the (S,S)-diastereomer 2b, compound 3, adopts a beta-bend conformation at the C-terminus, as already reported for 1. However, the backbone torsion angles [phi 2 = 57.4(4), psi 2 = -129.9(3) degrees; psi 3 = -92.3(4), phi 3 = 6.4(5) degrees] lie close to the values expected for the corner residues of an ideal type-II' beta-bend. A weak intramolecular 4----1 H-bond is seen between the Gly carboxyamide anti-NH and Pro C = O groups. In the newly formed 2,2,3,4-tetraalkyl-5-oxo-imidazolidin-1-yl moiety the psi 1 torsion angle is 12.9(4) degrees and the intramolecular N(3)...N(4) separation is 2.321(4)A.     

Design of peptides with alpha,beta-dehydro-residues: synthesis, and crystal and molecular structure of a 3(10)-helical tetrapeptide Boc-L-Val-deltaPhe-deltaPhe-L-Ile-OCH3.

The peptide Boc-L-Val-deltaPhe-deltaPhe-L-Ile-OCH3 was synthesized using the azlactone method in the solution phase, and its crystal and molecular structures were determined by X-ray diffraction. Single crystals were grown by slow evaporation from solution in methanol at 25 degrees C. The crystals belong to an orthorhombic space group P2(1)2(1)2(1) with a = 12.882(7) A, b = 15.430(5) A, c = 18.330(5) A and Z = 4. The structure was determined by direct methods and refined by a least-squares procedure to an R-value of 0.073. The peptide adopts a right-handed 3(10)-helical conformation with backbone torsion angles: phi1 = 56.0(6)degrees, psi1 = -38.0(6)degrees, phi2 = -53.8(6)degrees, psi2 = 23.6(6)degrees, phi3 = -82.9(6)degrees, psi3 = -10.6(7)degrees, phi4 = 124.9(5)degrees. All the peptide bonds are trans. The conformation is stabilized by intramolecular 4-->1 hydrogen bonds involving Boc carbonyl oxygen and NH of deltaPhe3 and CO of Val1 and NH of Ile4. It is noteworthy that the two other chemically very similar peptides: Boc-Val-deltaPhe-deltaPhe-Ala-OCH3 (i) and Boc-Val-deltaPhe-deltaPhe-Val-OCH3 (ii) with differences only at the fourth position have been found to adopt folded conformations with two overlapping beta-turns of types II and III', respectively, whereas the present peptide adopts two overlapping beta-turns of type III. Thus the introduction of Ile at fourth position in a sequence Val-deltaPhe-deltaPhe-X results in the formation of a 3(10)-helix. The crystal structure is stabilized by intermolecular hydrogen bonds involving NH of Val1 and carbonyl oxygen of a symmetry related (-x, y - 1/2, 1/2 + z) deltaPhe2 and NH of deltaPhe2 with carbonyl oxygen of a symmetry related (x, y1/2, 1/2 + z) Ile4. This gives rise to long columns of helical molecules linked head to tail running along [010] direction.     

Energy-minimized conformation of gramicidin-like channels. I. Infinitely long poly-(L,D)-alanine beta 6.3-helix.

The energy-minimized conformation of an infinitely long poly-(L,D)-alanine in single-stranded beta 6.3-helix was calculated by the molecular mechanics method. When energy minimization was started from a wide range of initial geometries, six optimized conformations were obtained and identified as the right- and left-handed counterparts of the beta 4.5-, beta 6.3-, and beta 8.2-helices. It was found that their conformation energies increase in this order, the beta 4.5-helix having the lowest energy. The backbone dihedral angles of the energy-minimized beta 6.3-helix were: phi L = -116 degrees (or -131 degrees), psi L = 122 degrees (or 111 degrees), phi D = 131 degrees (or 116 degrees), psi D = -111 degrees (or -122 degrees), omega L = 173 degrees (or 173 degrees), and omega D = -173 degrees (or -173 degrees) for the right-handed (or left-handed) helix. This helix was composed of 6.30 residues/turn with a pitch of 4.97 A. All the alpha-carbons of L- and D-configurations appeared on one common circular helix. Interestingly, small deviations (approximately 7 degrees) of the peptide bonds from the planar structure caused a considerable lowering of the conformation energy, and, at the same time, they produced more favorable fitting of the hydrogen bonds; the carbonyl oxygens and the nearest-neighbor alpha-hydrogens also took more favorable relative positions.     

Solution conformation of the branch points of N-linked glycans: synthetic model compounds for tri'-antennary and tetraantennary glycans

The solution conformation of model compounds for the tri'-antennary and tetraantennary (six-arm) branch point of N-linked glycans has been determined through the use of chemical shift, relaxation, and nuclear Overhauser enhancement data. The object was to establish the conformation about the glycosidic linkages in the N-linked substructure GlcNAc(beta 1,6) [GlcNAc(beta 1,2)] Man(alpha)- by estimation of values for the appropriate glycosidic torsional angles. The GlcNAc(beta 1,6) linkage in a trisaccharide model compound was found to be constrained to a narrow rotameric subpopulation about the substituted Man C5-C6 bond (omega = -60 degrees) and a narrow range of possible phi - psi values. Free rotation about the Man C5-C6 bond was obstructed by unfavorable steric interactions between the GlcNAc(beta 1,6) and GlcNAc(beta 1,2) residues. A phi, psi value of 55 degrees, 190 degrees was found to be consistent with the NMR data for the GlcNAc(beta 1,6) linkage. However, the value of psi appears to be "virtual" in that the molecule is in equilibrium between two different values (90 degrees and 252 degrees). For the GlcNAc(beta 1,2) linkage, complete agreement between all the observed NMR parameters and all the calculated ensemble average values could only be obtained with a set of potential energy functions which included hydrogen bonding. Other choices of potentials yielded calculated values that disagreed with at least two of the observed quantities. As a result, we infer that an interresidue hydrogen bond is formed, and we find it to be between the GlcNAc(beta 1,2) ring oxygen and the Man C3 hydroxyl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of water molecules in the crystal structure of gly-L-ala-L-phe: A possible sequence preference for nucleation of α-helix?

The synthetic peptide Gly-L-Ala-L-Phe (C14H19N3O4.2H2O; GAF) crystallizes in the monoclinic space group P2I1), with a = 5.879(1), b = 7.966(1), c = 17.754(2) A, beta = 95.14(2) degrees, Dx = 1.321 g cm-3, and Z = 2. The crystal structure was solved by direct methods using the program SHELXS-86 and refined to an R value of 0.031 for 1425 reflections (greater than 3 sigma). The tripeptide exists as a zwitterion in the crystal and assumes a near alpha-helical backbone conformation with the following torsion angles: psi 1 = -147.8 degrees; phi 2, psi 2 = -71.2 degrees, 33.4 degrees; phi 3, psi 3 = -78.3 degrees, -43.3 degrees. In this structure, one water molecule bridges the COO- and NH3+ terminii to complete a turn of an alpha-helix and another water molecule participates in head-to-tail intermolecular hydrogen bonding, so that the end result is a column of molecules that looks like an alpha-helix. Thus, the two water molecules of crystallization play a major role in stabilizing the near alpha-helical conformation of each tripeptide molecule and in elongating the helix throughout the crystal. An analysis of all protein sequences around regions containing a GAF fragment by Chou-Fasman's secondary structure prediction method showed that those regions are likely to assume an alpha-helical conformation with twice the probability they are likely to adopt a beta-sheet conformation. It is conceivable that a GAF fragment may be a good part of the nucleation site for forming alpha-helical fragments in a polypeptide, with the aqueous medium playing a crucial role in maintaining such transient species.