Crystal structures of two cyclic pseudopentapeptides containing ψ[CH2S] and ψ[CH2SO] backbone surrogates

The solid state conformations of cyclo[Gly–Proψ[CH₂S]Gly–D –Phe–Pro] and cyclo[Gly–Proψ[CH₂–(S)–SO]Gly–D –Phe–Pro] have been characterized by X-ray diffraction analysis. Crystals of the sulfide trihydrate are orthorhombic, P2₁2₁2₁, with a = 10.156(3) Å, b = 11.704(3) Å, c = 21.913(4) Å, and Z = 4. Crystals of the sulfoxide are monoclinic, P2₁, with a = 10.662(1) Å, b = 8.552(3) Å, c = 12.947(2) Å, β = 94.28(2), and Z = 2. Unlike their all-amide parent, which adopts an all-trans backbone conformation and a type II β-turn encompassing Gly-Pro-Gly-D -Phe, both of these peptides contain a cis Gly¹-Pro² bond and form a novel turn structure, i.e., a type II′ β-turn consisting of Gly–D –Phe–Pro–Gly. The turn structure in each of these peptides is stabilized by an intramolecular H bond between the carbonyl oxygen of Gly¹ and the amide proton of D -Phe⁴. In the cyclic sulfoxide, the sulfinyl group is not involved in H bonding despite its strong potential as a hydrogen-bond acceptor. The crystal structure made it possible to establish the absolute configuration of the sulfinyl group in this peptide. The two crystal structures also helped identify a type II′ β-turn in the DMSO-d₆ solution conformers of these peptides. © 1993 John Wiley & Sons, Inc.     

Deuterium NMR investigation of backbone dynamics in the synthetic oligonucleotide [d(CGCGAATTCGCG)]2

Backbone dynamics in the [5',5"-2H2]2'-deoxythymidine labeled duplex dodecamer [d-(CGCGAAT*T*CGC)]2 have been investigated by solid-state 2H NMR. Quadrupolar echo line shapes, spin-lattice relaxation, and quadrupolar echo decay times were obtained over hydration levels ranging from W = 0.0 to 25.2 (moles of H2O/mole of nucleotide). Variation of the line shape with changing hydration level was analyzed by using models employed in previous investigations of dodecamer base and sugar dynamics. Both fast local motions and a slower helix motion were present within the oligonucleotide. The fast motion was modeled as a four-site libration whose amplitude increased with hydration level. The root mean square amplitude of this librational model was 2-6 degrees larger than the amplitude observed in either the furanose ring or base labeled material for the entire range of hydration levels investigated. The observed line shape was inconsistent with a rapid three-site trans-gauche isomerization. A slow motion about the helix axis was observed at low water levels and increased in rate and amplitude with hydration. This motional model is in agreement with previous oligonucleotide studies.     

Morphiceptin and beta-casomorphin-5 analogues containing a reduced peptide bond: selective mu-receptor agonists and a novel mu antagonist, H-Tyr-Pro psi (CH2-NH)Phe-Pro-Gly-OH.

In order to prevent enzymatic degradation of beta-casomorphin-5 (1) and morphiceptin, reduced peptide bonds were incorporated at the 2-3 and 3-4 bonds, respectively. The analogues were synthesized by a combination of solid phase methodology and reductive alkylation of resin-bound peptide amines with Boc-amino acid aldehydes (Boc: tert-butyloxycarbonyl) in the presence of NaBH3CN. During reversed phase high pressure liquid chromatography purification, peak shape distortions could be observed. Epimerization was excluded, based on gas chromatography/mass spectroscopy analysis, which indicated acceptable levels of racemization (less than 3%) in the crude product. Instead, the phenomena could be attributed to slow cis/trans isomerizations originating from the Xxx-Pro bonds in the sequence. The presence of different conformational isomers was also established by 1H-nmr spectroscopy in DMSO-d6. All analogues showed high stability in blood plasma, enhanced binding affinity for the mu receptor, and very low binding to the delta receptor. While the Phe 3 psi(CH2-N)Pro4 analogues (3) and (5) displayed agonist activity, the Pro 2 psi(CH2-NH)Phe3 modified analogue (2) showed antagonist activity comparable to D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2.     

Stereoselective synthesis of Psi[CH(2)O] pseudodipeptides and conformational analysis of a PhePsi[CH(2)O]Ala containing analogue of the drug desmopressin

A method for synthesis of XaaPsi[CH(2)O]Ala/Gly pseudodipeptides in good yields and excellent diastereoselectivity from azido alcohols and (R)-2-chloropropionic acid or tert-butyl bromoacetate has been developed. Insertion of one of the pseudodipeptide building blocks in the peptide drug desmopressin revealed that methylene ether isosteres may have only a minor influence on the secondary structure of peptides.     

Synthesis and binding characteristics of [3H] H-Tyr-Ticpsi[CH2-NH] Cha-Phe-OH, a highly specific and stable delta-opioid antagonist.

Substitution of the Phe3 aromatic ring in H-Tyr-Ticpsi[CH2-NH]Phe-Phe-OH with cyclohexylalanine (Cha) has been reported to result in a compound, H-Tyr-Ticpsi[CH2-NH]Cha-Phe-OH (TICP[psi]), showing substantially increased delta-opioid antagonist potency and high delta selectivity. TICP[psi] was radiolabeled by catalytic tritiation of its precursor Tyr(3',5'-I2)1TICP[psi]. Binding characteristics of the new tritiated pseudopeptide were determined using the radioligand binding assay in rat brain membranes. On the basis of the results of saturation binding studies performed at 25 degrees C, an equilibrium dissociation constant (Kd) of 0.35 nM and a receptor density (Bmax) of 112 fmol/mg protein were calculated. This new tritiated ligand exhibits high affinity for delta-opioid receptors, whereas its binding to mu and kappa receptors is weak. A study of [H3]TICP[psi] binding displacement by various receptor-selective opioids showed the following rank order of potency: delta > kappa = mu. These receptor binding characteristics of the ligand, together with its high specific radioactivity (41.3 Ci/mmol) and stability, makes it a useful tool for labeling delta-opioid receptors, both in vitro and in vivo.     

The trans labilization of cis-[PtCl2(13CH3NH2)2] by glutathione can be monitored at physiological pH by [1H,13C] HSQC NMR

In order to monitor the trans labilization of cisplatin at physiological pH we have prepared the complex cis-[PtCl₂(¹³CH₃NH₂)₂] and studied its interactions with excess glutathione in aqueous solution at neutral pH by two-dimensional [1H,13C] heteronuclear single-quantum correlation (HSQC) NMR spectroscopy. [1H,13C] HSQC spectroscopy is a good method for following the release of ¹³CH₃NH₂ but is not so good for characterizing the Pt species in solution. In the reaction of cisplatin with glutathione, Pt–S bonds are formed and Pt–NH₃ bonds are broken. The best technique for following the formation of Pt–S bonds of cisplatin is by UV spectroscopy. [1H,13C] HSQC spectroscopy is the best method for following the breaking of the Pt–N bonds. [1H,15N] HSQC spectroscopy is the best method for characterizing the different species in solution. However, the intensity of the peaks in the ¹⁵NH₃–Pt–S region, in [1H,15N] HSQC, reflects a balance between the formation of Pt–S bonds, which increases the signal intensity, and the trans labilization, which decreases the signal intensity. [1H,15N] HSQC spectroscopy and [1H,13C] HSQC spectroscopy are complementary techniques that should be used in conjunction in order to obtain the most accurate information on the interaction of platinum complexes with sulfur-containing ligands.     

An NMR investigation of the conformational equilibria of 2-(2'-pyridyl)ethylphosphonic acid in several solvents

Vicinal proton-proton NMR couplings have been used to investigate whether the position of conformational equilibria is determined by intramolecular N-H hydrogen bonding for 2-(2'-pyridyl)ethylphosphonic acid 1 in its various possible ionization states in water, methanol, ethanol, and dimethyl sulfoxide (DMSO). With 1 in the form of its monoanion and dianion, the trans is favored, with the dianion being more trans than the monoanion for a given solvent, probably as the result of steric effects, possibly enhanced by repulsive electrostatic effects between the negatively charged phosphonic group and the lone pair on the pyridine nitrogen. For 1 and its conjugate acid, the gauche amounts, respectively, to 43% and 45% in water, 66% and 51% in methanol, 66% and 64% in ethanol, and 29% and 49% in DMSO. For these latter two species, electrostatic, steric, and hydrogen bonding-effects are all likely to play a role in determining the conformational equilibria.     

Endomorphin 1[psi] and endomorphin 2[psi], endomorphins analogues containing a reduced (CH2NH) amide bond between Tyr1 and Pro2, display partial agonist potency but significant antinociception

Endomorphin 1 (EM1) and endomorphin 2 (EM2) are highly potent and selective mu-opioid receptor agonists and have significant antinociceptive action. In the mu-selective pocket of endomorphins (EMs), Pro2 residue is a spacer and directs the Tyr1 and Trp3/Phe3 side chains into the required orientation. The present work was designed to substitute the peptide bond between Tyr1 and Pro2 of EMs with a reduced (CH2NH) bond and study the agonist potency and antinociception of EM1[psi] (Tyr[psi(CH2NH)]Pro-Trp-Phe-NH2) and EM2[psi] (Tyr[psi(CH2NH)]Pro-Phe-Phe-NH2). Both EM1[psi] and EM2[psi] are partial mu opioid receptor agonists showing significant loss of agonist potency in GPI assay. However, EMs[psi] exhibited potent supraspinal antinociceptive action in vivo. In the mice tail-flick test, EMs[psi] (1, 5, 10 nmol/mouse, i.c.v.) produced potent and short-lasting antinociception in a dose-dependent and naloxone (1 mg/kg) reversed manner. At the highest dose of 10 nmol, the effect of EM2[psi] was prolonged and more significant than that of EM2. In the rat model of formalin injection induced inflammatory pain, EMs[psi] (0.1, 1, 10 nmol/rat, i.c.v.), like EMs, exerted transient but not dose-dependent antinociception. These results suggested that in the mu-selective pocket of EMs, the rigid conformation induced by the peptide bond between Tyr1 and Pro2 is essential to regulate their agonist properties at the mu opioid receptors. However, the increased conformational flexibility induced by the reduced (CH2NH) bond made less influence on their antinociception.     

Solvent cage effects: the influence of radical mass and volume on the recombination dynamics of radical cage pairs generated by photolysis of [CpCH2CH2N(CH3)C(O)(CH2)nCH3Mo(CO)3]2 (n = 3, 8, 13, 18) (Cp = eta 5-C5H4) complexes

The photochemistry of the [(CpR)Mo(CO)(3)](2) molecules, where CpR = eta(5)-C(5)H(4)(CH(2))(2)C(O)NCH(3)(CH(2))(n)CH(3) (n = 3, 8, 13, and 18), was examined using femtosecond pump-probe transient absorption spectroscopy. The goal of this study was to investigate the importance of radical size and mass on the dynamics and efficiency of geminate radical-radical recombination. The femtosecond results demonstrated the lack of any size/mass dependence of the recombination efficiency. This finding contrasts with results from a prior study that did find a size/mass dependence using a steady-state photochemical technique. To explain these conflicting results, it is proposed that the femtosecond pump-probe results are a measurement of the efficiency of primary geminate recombination whereas the steady-state method results are a measurement of the sum of primary and secondary geminate recombination efficiencies. The size/mass dependence is evident in the latter because secondary geminate recombination is a slower diffusive recombination process and therefore depends on the steric properties of the radicals. Although the existence of primary and secondary recombination channels is often taken for granted, experimental differentiation of primary and secondary caging has proven to be difficult because it is not possible for a single experimental technique to span the entire timescale for recombination of a radical cage pair and adequately resolve these recombination pathways.     

Effects of [Nphe1]nociceptin(1-13)NH2, [Phe1(CH2-NH)Gly2]nociceptin(1- 13)NH2, and nocistatin on nociceptin inhibited constrictions of guinea pig isolated bronchus

Electric field stimulation (EFS) causes excitatory non adrenergic-non cholinergic (eNANC) and cholinergic constrictions in the guinea pig isolated bronchus, the activation of eNANC and cholinergic nerves respectively. We investigated the effects of [Nphe1]nociceptin(1-13)NH2 ([Nphe1]NC(1-13)NH2), [Phe1(CH2-NH)Gly2]nociceptin(1- 13)NH2 ([F/G] NC(1-13)NH2), and nocistatin (NST) on nociceptin (NC) inhibited constrictions in isolated bronchus of guinea pig. The results show that NC (1 micromol/L) inhibited EFS-induced eNANC and cholinergic constrictions compared with the control, in which nociceptin was not applied. After pretreatment with [Nphe1]NC(1-13)NH2, [F/G]NC(1-13)NH2, or NST, the inhibitions of NC were antagonized by [Nphe1]NC(1-13)NH2 and [F/G]NC(1-13)NH2 but not NST. However, [Nphe1]NC(1-13)NH2, [F/G]NC(1-13)NH2, and NST did not affect the inhibitions induced by morphine. Furthermore, [Nphe1]NC(1-13)NH2, [F/G]NC(1-13)NH2 and NST did not cause any appreciable effects on EFS-induced eNANC and cholinergic constrictions in guinea pig bronchi. The results demonstrate that [Nphe1]NC(1-13)NH2 and [F/G]NC(1- 13)NH2 but not NST act as selective antagonists of the NC receptor and the effects of NC on EFS-induced constrictions of guinea pig isolated bronchus.     

Optical activity of dimolybdenum complex induced by chiral,chelating diamine ligand; syntheses and structures of [Mo2(O2CCF3)2(S,S-dach)2(CH3CN)2][BF4]2 and [Mo2(O2CCF3)2(R,R-dach)2(CH3CN)2][BF4]2 (dach=1,2-diaminocyclohexane)

The first structurally characterized, quadruply bonded complexes containing chiral diamine ligands, [Mo₂(O₂CCF₃)₂(S,S-dach)₂(CH₃CN)₂][BF₄]₂ (1), and [Mo₂(O₂CCF₃)₂(R,R-dach)₂(CH₃CN)₂][BF₄]₂ (2); (dach=1,2-diaminocyclohexane) were prepared by reactions of [Mo₂(O₂CCF₃)₂(CH₃CN)₆][BF₄]₂ with S,S-dach and R,R-dach, respectively, in CH₃CN. Their UV–Vis and circular dichroism (CD) spectra have been recorded and their structures determined by X-ray crystallography. Crystals of complexes 1 and 2 conform to the space groups P2 with two independent half molecules in the asymmetric unit. The two molecules have a similar structure consisting of a Mo₂ unit bridged by two cis-trifluoroacetate ligands and chelated by two dach ligands. Two acetonitrile molecules are coordinated to the Mo centers along the MoMo bond. The absorption wavelength at 507 nm for both 1 and 2 can be assigned to δ_xy→δ_xy* transitions. The solution CD spectra of these two complexes show two prominent bands at 525 and 385 nm and form mirror images of each other. The solid CD spectra of complexes 1 and 2 show marked red-shift in the absorption energies as compared with those measured in solution. The one-electron static coupling mechanism was invoked to explain the CD spectra for these complexes and the second lowest energy bands were assigned to be δ_xy→δ_x²−y² transitions.     

An AB initio investigation of molecules with a disulfide bond: (HS)2, (CH3S)2 and cystine

ab initio Calculations at the Gaussian-70 STO-3G and 4-31G basis levels have been carried out for (HS)2 and (CH3S)2. Cystine was investigated at the STO-3G level. The STO-3G energy minimized geometry agrees well with experiments for (HS)2 and (CH3S)2. The barriers to internal rotation are predicted to be (at the 4.31G level): (HS)2, cis 8.5 kcal, trans 3.03 kcal; (CH3S)2, cis 18.47 kcal, trans 6.04 kcal.     

Design of a new peptidomimetic agonist for the melanocortin receptors based on the solution structure of the peptide ligand,Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2)

The solution structure of a potent melanocortin receptor agonist, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2) (1) was calculated using distance restraints determined from 1H NMR spectroscopy. Eight of the lowest energy conformations from this study were used to identify non-peptide cores that mimic the spatial arrangement of the critical tripeptide region, DPhe-Arg-Trp, found in 1. From these studies, compound 2a, containing the cis-cyclohexyl core, was identified as a functional agonist of the melanocortin-4 receptor (MC4R) with an IC(50) and EC(50) below 10 nM. Compound 2a also showed 36- and 7-fold selectivity over MC3R and MC1R, respectively, in the binding assays. Subtle changes in cyclohexane stereochemistry and removal of functional groups led to analogues with lower affinity for the MC receptors.     

An unexpected ‘4+2’ [N3S]/[NS] rhenium(IV) complex formed upon cleavage of a Re(V) imido bond

The reaction of [Re(NMe)Cl₃(PPh₃)₂] with the pentadentate [N₃S₂] ligand pyN₂H₂S₂---H₂ [2,6-bis(2-mercaptophenylamino)dimethylpyridine] (1) in the presence of triethylamine did not yield the anticipated six-coordinate complex [Re(NMe)(η⁵-pyN₂HS₂)] (2), but rather resulted in cleavage of the Re(V)=NMe bond. A novel six-coordinate Re(IV) [N₃S]/[NS] complex [Re(η⁴-SC₆H₄---2-NCH₂---C₅H₃N---C=NC₆H₄---2-S)(η²-NHC₆H₄---2-S)] (4) was thus obtained with the simultaneous coordination of 2-aminothiophenol, a dianionic bidentate [NS] donor resulting from the decomposition of the parent ligand and ligand 3, a dianionic tetradentate [N₃S] donor formed by partial self-condensation and subsequent oxidation of the parent ligand 1. Crystal data for 4: C₂₅H₁₈N₄S₃Re·CH₂Cl₂, monoclinic, space group P2₁/n, a=9.255(2) Å, b=11.181(2) Å, c=25.316(4) Å, β=97.434(3)°, V=2587.8(7) Å³ and Z=4.     

Ligand reactivity in polypyridine complexes; [Ru(bipy)3]n+ analogs incorporating pendant polyamine substituents

The complex cation [Ru(bipy)₂L]²⁺ (bipy = 2,2′- bipyridine, L = 4,4′-dichloro-2,2′-bipyridine) is activated towards nucleophilic substitution of chloride. Reactions of [Ru(bipy)₂L]²⁺ with potentially polydentate amines give rise to novel derivatives [Ru(bipy)₂L′]²⁺ which possess a central redox and photochemically active ‘Ru(bipy)3’ core, and a potentially multidentate periphery for coordination to other metal centres.     

Conformational analysis of β-methyl-para-nitrophenylalanine stereoisomers of cyclo[D-Pen2, D-Pen5]enkephalin by NMR spectroscopy and conformational energy calculations

Solution conformations of β-methyl-para-nitrophenylalanine⁴ analogues of the potent δ-opioid peptide cyclo[D-Pen², D-Pen⁵]enkephalin (DPDPE) were studied by combined use of nmr and conformational energy calculations. Nuclear Overhauser effect connectivities and ³J_HNC^α_H coupling constants measured for the (2S, 3S)-, (2S, 3R)-, and (2R, 3R)-stereoisomers of[β-Me-p-NO₂Phe⁴]DPDPE in DMSO were compared with low energy conformers obtained by energy minimization in the Empirical Conformational Energy Program for Peptides #2 force field. The conformers that satisfied all available nmr data were selected as probable solution conformations of these peptides. Side-chain rotamer populations, established using homonuclear (³J_H^α_H^β) and heteronuclear (³J_H^αC^γ) coupling constants and ¹³C chemical shifts, show that the β-methyl substituent eliminates one of the three staggered rotamers of the torsion angle x¹ for each stereoisomer of the β-Me-p-NO₂Phe⁴. Similar solution conformations were suggested for the L-Phe⁴-containing (2S, 3S)- and (2S, 3R)-stereoisomers. Despite some local differences, solution conformations of L- and D-Phe⁴-containing analogues have a common shape of the peptide backbone and allow similar orientations of the main δ-opioid pharmacophores. This type of structure differs from several models of the solution conformations of DPDPE, and from the model of biologically active conformations of DPDPE suggested earlier. The latter model is allowed for the potent (2S, 3S)- and (2S, 3R)-stereoisomers of [β-Me-p-NO₂Phe⁴] DPDPE, but it is forbidden for the less active (2R, 3R)- and (2R, 3S)-stereoisomers. It was concluded that the biologically active stereoisomers of [β-Me-p-No₂Phe⁴] DPDPE in the δ-receptor-bound state may assume a conformation different from their favorable conformations in DMSO. © 1996 John Wiley & Sons, Inc.     

The nature of stabilization of the tandem DNA duplex pTGGAGCTG (pCAGC + (Phn-NH-(CH2)3-NH)pTCCA) based on the UV-, CD-, and two-dimensional NMR spectroscopy data

Properties and three-dimensional structure of the tandem DNA duplex pTGGAGCTG.(pCAGC+(PhnL)pTCCA) in aqueous solution, where L is an amino linker and Phn is an N-(2-hydroxyethyl)phenazinium residue, were studied spectrophotometrically and by two-dimensional 1H NMR spectroscopy (COSY and NOESY). When a tandem complex involving a Phn residue-bearing oligonucleotide is formed, the dye aromatic system intercalates into the double helix at the nick site and takes part in two stacking interactions: a strong one (3.5-4 A) with the T5-A12 base pair of its own duplex moiety and a weak one (4-5 A) with the C4-G13 pair of the adjoining duplex (mainly with the C4 base). This arrangement of the dye residue, providing a cross-interaction of the phenazinium moiety with the base pairs of the adjacent duplex structures, results in the stabilization of the whole tandem complex.     

An NMR study of the lactonization of alpha-N-acetylneuraminyl-(2 --> 3)-lactose

The composition of the products formed by treatment of commercial alpha-Neu5Ac-(2 --> 3)-beta-D-Galp-(1 --> 4)-D-Glc (3'-sialyllactose) with glacial acetic acid was investigated by 1H-13C one- and two-dimensional NMR spectroscopy and fast atom bombardment-mass spectrometry. The data confirmed that the major product of the reaction was alpha-Neu5Ac-(2 --> 3)-beta-D-Galp-(1 --> 4)-D-Glc-(1c --> 2b)-lactone, which reverted to the starting material on standing in aqueous solution at ambient temperature, but for which complete NMR assignments are reported. The NMR data led to the tentative conclusion that the reaction also yielded small amounts of lactose, and alpha-Neu5Ac-(2 --> 3)-beta-D-Galp-(1 --> 4)-D-Glc-(1c --> 4b)-lactone which was stable in aqueous solution.     

Self-assembling diblock copolymers of poly[N-(2-hydroxypropyl)methacrylamide] and a beta-sheet peptide

The self-assembly of hybrid diblock copolymers composed of poly(HPMA) and beta-sheet peptide P11 (CH(3)CO-QQRFQWQFEQQ-NH(2)) blocks was investigated. Copolymers were synthesized via thiol-maleimide coupling reaction, by conjugation of semitelechelic poly(HPMA)-SH with maleimide-modified beta-sheet peptide. As expected, CD and CR binding studies showed that the peptide block imposed its beta-sheet structural arrangement on the structure of diblock copolymers. TEM and AFM proved that peptide and these copolymers had the ability to self-assemble into fibrils.     

A novel synthesis of alpha-D-Galp-(1-->3)-beta-D-Galp-1-O-(CH2)3-NH2, its linkage to activated matrices and absorption of anti-alphaGal xenoantibodies by affinity columns

Pig organs transplanted into primates are rapidly rejected because of the interaction between Gal alpha(1-->3)Gal epitopes carried by the graft and natural antibodies (anti-alphaGal antibodies) present in the blood of the recipient. This report describes a simplified synthesis of the xenogeneic disaccharide and its linkage to activated gel matrices. The digalactosides alpha-D-Galp-(1-->3)-alpha,beta-D-Galp-OAll were synthesized by the condensation of the trichloroacetimidoyl 2,3,4,6-tetra-O-benzyl-beta-D-galactopyranoside donor with the 3,4-unprotected allyl 2,6-di-O-benzyl-alpha- or beta-D-galactopyranoside acceptor precursor. Deallylation and hydrogenolysis led to the free digalactoside, whereas hydrogenolysis alone resulted in the 1-O-propyl digalactoside. Both products were tested by inhibition ELISA of natural anti-Gal alpha(1-->3)Gal antibodies. The alpha-D-Galp-(1-->3)-beta-D-Galp-OPr was found to be the best inhibitor. Thus, the allyl group of the partially benzylated alpha-D-Galp-(1-->3)-beta-D-Galp-OAll was engineered, via the hydroxy-, the tosyloxy- and the azidopropyl intermediates, into an aminopropyl group amenable to binding to N-hydroxysuccinimide-activated agarose gel matrices in order to obtain specific immunoabsorption columns. Columns made of gel substituted with 5 micromol of disaccharide per milliliter were found efficient for the immunoabsorption of anti-alphaGal antibodies from human plasma.