Studies on epimeric D-xylo-and D-lyxo-tetritol-1-yl-2-phenyl-2H-1,2,3-triazoles. Synthesis and anomeric configuration of 4-(alpha-and beta-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs

Treatment of 4-(D-xylo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazole (1) with one mole equivalent of tosyl chloride in pyridine solution, afforded the C-nucleoside analog; 4-(beta-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole (2) in 55% yield, as well as the byproduct 4-(4-chloro-4-deoxy-D-xylo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazo le (4). Treatment of the epimeric 4-(D-lyxo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazole (6) with tosyl chloride in pyridine solution afforded the anomeric C-nucleoside analog; 4-(alpha-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole (7) in 29% yield, as well as the byproduct 4-(4-chloro-4-deoxy-D-lyxo-tetritol-1-yl)-2-phenyl-2H-1,2,3- triazole (9). Similar treatment of 1 and 6 with trifluoromethanesulfonyl chloride in pyridine solution afforded 2 and 7, respectively. The structure and anomeric configuration of these compounds were determined by acetylation, NMR, NOE, and circular dichroism spectroscopy, as well as mass spectrometry.     

Enhanced CO2 fixation by a non-photosynthetic microbial community under anaerobic conditions: optimization of electron donors

To enhance the CO(2) fixation efficiency of the non-photosynthetic microbial community (NPMC) isolated from sea water under anaerobic conditions without hydrogen, the concentration of inorganic compounds as electron donors and their ratios were optimized by response surface methodology design (RSMD). The results indicated that the CO(2) fixation efficiency of NPMC using NaNO(2), Na(2)S(2)O(3) and Na(2)S as the electron donors was increased about 90%, 75% and 207%, respectively. Additionally, there were interactions between two electron donors and three electron donors. Central composite RSMD experimentation predicted that the optimal concentration and ratios of these inorganic compounds was 1.04% NaNO(2), 1.07% Na(2)S(2)O(3) and 0.98% Na(2)S. Under these conditions, the fixed CO(2) was 139.89 mg/L, which obviously exceeded the amount prior to optimization, as well as when H(2) was used as an electron donor. The established electron donor system can effectively enhance the CO(2) fixation efficiency of NPMC without hydrogen under anaerobic conditions.     

Effects of 19-hydroxy-prostaglandins on oviductal and uterine motility.

The effects of 19-hydroxyprostaglandins (19-OH-PGs) were tested in vivo on the rabbit oviduct and uterus and on the rhesus monkey (Macaca mulatta) uterus. The 19-OH-PGEs suppressed spontaneous oviductal and uterine activity in the rabbit. The qualitative effect on the rabbit oviduct of 19-OH-PGEs was similar to that of PGE2. However, the typical response of the rabbit uterus to PGE2 was an increase in muscle activity. With regard to the rabbit oviduct, 19(R)-OH-PGE2 was as potent as PGE2, but 19(S)-OH-PGE2 was approximately 1/2 as potent as PGE2. Based on the dose of 19-OH-PGEs usually required to cause a minimal suppression and the dose of PGE2 required to cause a minimal stimulation of rabbit uterine activity, 19(R)-OH-PGE2 was twice as potent as PGE2 while 19(S)-OH-PGE2 was 1/2 as potent as PGE2. Stimulatory effects on the rabbit oviduct and uterus were observed following administration of 19-OH-PGFs and PGF2alpha. The potency on the rabbit oviduct of 19(S)-OH-PGF2alpha was about 1/5 to 1/10 that of PGF2alpha; the potency of 19(R)-OH-PGF2alpha was about 1/10 to 1/20 that of PGF2alpha. Both 19-OH-PGFs were approximately 1/5 to 1/10 as potent as PGF2alpha on the rabbit uterus. At the doses tested 19-OH-PGFs were inactive on the monkey uterus. Thus, these compounds are at least 1/5 as active as PGF2alpha. In contrast, 19(R)-OH-PGE2 had approximately the same potency as PGE2 in stimulating monkey uterine activity; but 19(S)-OH-PGE2 was approximately 1/3 as potent as PGE2.     

Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose

LTRPC2 is a cation channel recently reported to be activated by adenosine diphosphate-ribose (ADP-ribose) and NAD. Since ADP-ribose can be formed from NAD and NAD is elevated during oxidative stress, we studied whole cell currents and increases in the intercellular free calcium concentration ([Ca(2+)](i)) in long transient receptor potential channel 2 (LTRPC2)-transfected HEK 293 cells after stimulation with hydrogen peroxide (H(2)O(2)). Cation currents carried by monovalent cations and Ca(2+) were induced by H(2)O(2) (5 mm in the bath solution) as well as by intracellular ADP-ribose (0.3 mm in the pipette solution) but not by NAD (1 mm). H(2)O(2)-induced currents developed slowly after a characteristic delay of 3-6 min and receded after wash-out of H(2)O(2). [Ca(2+)](i) was rapidly increased by H(2)O(2) in LTRPC2-transfected cells as well as in control cells; however, in LTRPC2-transfected cells, H(2)O(2) evoked a second delayed rise in [Ca(2+)](i). A splice variant of LTRPC2 with a deletion in the C terminus (amino acids 1292-1325) was identified in neutrophil granulocytes. This variant was stimulated by H(2)O(2) as the wild type. However, it did not respond to ADP-ribose. We conclude that activation of LTRPC2 by H(2)O(2) is independent of ADP-ribose and that LTRPC2 may mediate the influx of Na(+) and Ca(2+) during oxidative stress, such as the respiratory burst in granulocytes.     

Studies of Mg2+/Ca2+ complexes of naturally occurring dinucleotides: potentiometric titrations, NMR, and molecular dynamics

Dinucleotides (Np(n)N'; N and N' are A, U, G, or C, n = 2-7) are naturally occurring physiologically active compounds. Despite the interest in dinucleotides, the composition of their complexes with metal ions as well as their conformations and species distribution in living systems are understudied. Therefore, we investigated a series of Mg(2+) and Ca(2+) complexes of Np(n)N's. Potentiometric titrations indicated that a longer dinucleotide polyphosphate (N is A or G, n = 3-5) linker yields more stable complexes (e.g., log K of 2.70, 3.27, and 3.73 for Ap(n)A-Mg(2+), n = 3, 4, 5, respectively). The base (A or G) or ion (Mg(2+) or Ca(2+)) has a minor effect on K(M)(ML) values. In a physiological medium, the longer Ap(n)As (n = 4, 5) are predicted to occur mostly as the Mg(2+)/Ca(2+) complexes. (31)P NMR monitored titrations of Np(n)N's with Mg(2+)/Ca(2+) ions showed that the middle phosphates of the dinucleotides coordinate with Mg(2+)/Ca(2+). Multidimensional potential of mean force (PMF) molecular dynamics (MD) simulations suggest that Ap(2)A and Ap(4)A coordinate Mg(2+) and Ca(2+) ions in both inner-sphere and outer-sphere modes. The PMF MD simulations additionally provide a detailed picture of the possible coordination sites, as well as the cation binding process. Moreover, both NMR and MD simulations showed that the conformation of the nucleoside moieties in Np(n)N'-Mg(2+)/Ca(2+) complexes remains the same as that of free mononucleotides.     

The difluoromethylenesulfonic acid group as a monoanionic phosphate surrogate for obtaining PTP1B inhibitors

Three peptides, 7-9, bearing sulfono(difluoromethyl)phenylalanine (F(2)Smp, 2), a nonhydrolyzable, monoanionic phosphotyrosine mimetic, were prepared and evaluated as PTP1B inhibitors. The most effective inhibitor was the nonapeptide, ELEF(F(2)Smp)MDYE-NH(2), (9) which exhibited a K(i) of 360 nM. A comparison of F(2)Smp-bearing peptides 7 [DADE(F(2)Smp)LNH(2), K(i)=3.4 microM] and 8 [EEDE(F(2)Smp)LNH(2), K(i)=0.74 microM] with their phosphono(difluoromethyl)phenylalanine (F(2)Pmp)-bearing analogues indicated that F(2)Smp is not as effective a pTyr mimetic as F(2)Pmp by 100- to 130-fold. Although F(2)Smp is not as effective as F(2)Pmp, a comparison of peptide 7 with analagous peptides bearing other monoanionic pTyr mimetics recently reported in the literature indicates that F(2)Smp is about 65-fold more effective than any other non-hydrolyzable, monanionic pTyr mimetic reported to date. To further assess the difluoromethylenesulfonic acid (DFMS) group as a monoanionic phosphate mimetic, a series of 24 nonpeptidyl biaryl compounds bearing the DFMS group were prepared using polymer-supported methodologies and screened for PTP1B inhibition. Several of these compounds were selected for further study and their IC(50)'s compared to their difluoromethylenephosphonic (DFMP) analogues. The differences in IC(50)'s between the DFMS and DFMP non-peptidyl compounds was not as great as with the F(2)Smp- and F(2)Pmp-bearing peptides. Possible reasons for this and its implication to the design of small molecule PTP1B inhibitors is discussed.     

Enhancement of Overgrowth by Gene Interactions in Lethal(2)giant Discs Imaginal Discs from Drosophila Melanogaster

Recessive lethal mutations of the lethal(2)giant discs (l(2)gd) and lethal(2)fat (l(2)ft) loci of Drosophila melanogaster cause imaginal disc hyperplasia during a prolonged larval stage. Imaginal discs from l(2)ft l(2)gd or Gl(2)gd double homozygotes show more extensive overgrowth than in either single homozygote, and double homozygous l(2)ft l(2)gd mitotic clones in adult flies show much more overgrowth than is seen in clones homozygous for either l(2)gd or l(2)ft alone. dachsous (ds) also acts as an enhancer of l(2)gd, producing dramatically overgrown discs and causing failure to pupariate in double homozygotes. The comb gap (cg) mutation, which also interacts with ds, greatly enhances the tendency of imaginal discs from l(2)gd larvae to duplicate as they overgrow. If l(2)gd homozygotes are made heterozygous for l(2)ft, then several discs duplicate, indicating that l(2)ft acts as a dominant enhancer of l(2)gd. l(2)ft also acts as a dominant enhancer of l(2)gd, and conversely l(2)gd acts as a dominant modifier of l(2)ft. The enhancement of overgrowth caused by various mutant combinations is accompanied by changes in expression of Decapentaplegic and Wingless. These results show that tumor suppressor genes act in combination to control cell proliferation, and that tissue hyperplasia can be associated with ectopic expression of genes involved in pattern formation.     

The interaction of native DNA with dimethyltin(IV) species

The reaction of aqueous native DNA (calf thymus) with the solvated organotin(IV) species [(CH3)2SnCl2(C2H5OH)n], as well as with [(CH3)2Sn(OH)(H2O)n]+ and (CH3)2Sn(OH)2 (i.e., the hydrolysis products of aqueous (CH3)2SnCl2 at pH approximately 5 and pH approximately 7.4 respectively), was investigated by 119Sn M?ssbauer spectroscopy. The addition of [(CH3)2SnCl2(C2H5OH)n] to DNA yielded a solid product, possibly (CH3)2Sn(DNA phosphodiester)2, where the environment of the tin atom is trans-octahedral with linear CSnC skeleton, and the equatorial atoms may consist of oxygen or nitrogen from water as well as from the nucleic acid constituents. No interaction with DNA apparently takes place due to hydrolyzed dimethyltin(IV) species, which occur in aqueous phases at approximate physiological pH values. The reaction pathway is then assumed to require weakly solvated, easily dissociable species such as [(CH3)2SnCl2(C2H5OH)n], which would imply in vivo reactivity of cellular DNA with organotins from hydrophobic sites.     

Neisseria gonorrhoeae DNA recombination and repair enzymes protect against oxidative damage caused by hydrogen peroxide

The strict human pathogen Neisseria gonorrhoeae is exposed to oxidative damage during infection. N. gonorrhoeae has many defenses that have been demonstrated to counteract oxidative damage. However, recN is the only DNA repair and recombination gene upregulated in response to hydrogen peroxide (H(2)O(2)) by microarray analysis and subsequently shown to be important for oxidative damage protection. We therefore tested the importance of RecA and DNA recombination and repair enzymes in conferring resistance to H(2)O(2) damage. recA mutants, as well as RecBCD (recB, recC, and recD) and RecF-like pathway mutants (recJ, recO, and recQ), all showed decreased resistance to H(2)O(2). Holliday junction processing mutants (ruvA, ruvC, and recG) showed decreased resistance to H(2)O(2) resistance as well. Finally, we show that RecA protein levels did not increase as a result of H(2)O(2) treatment. We propose that RecA, recombinational DNA repair, and branch migration are all important for H(2)O(2) resistance in N. gonorrhoeae but that constitutive levels of these enzymes are sufficient for providing protection against oxidative damage by H(2)O(2).     

Ni2+高效结合肽的筛选与作用研究

利用噬菌体随机十二肽库和金属亲和层析对重金属Ni2 进行结合肽筛选。经4轮生物淘洗、噬菌体扩增和DNA测序,获得一组多肽序列。GenBank Blast分析未发现同源序列,Clustal W多重序列比对也未找到Ni2 金属结合肽结合基序,但可能含有多聚组氨酸(His)2-5。噬菌体单克隆金属离子螯合树脂的亲和力测定和反筛、抑菌解毒试验表明:展示有金属结合肽的噬菌体不仅对Ni2 具有高亲和力,而且对其它金属离子也有作用,Cu2 、Ni2 、Co2 、Zn2 等金属离子对金属结合肽的亲和力显著高于Cd2 和Cr2 ,展示金属结合肽的噬菌体对重金属Ni2 具有一定的耐受和解毒作用。显微形态学观察也显示金属结合肽与金属螯合树脂的作用。对于了解重金属与多肽的相互作用机理以及环境重金属修复等均具有重要意义和价值。     

Selective cell death by water-soluble Fe-porphyrins with superoxide dismutase (SOD) activity

We investigated the effect on cell death of reactive oxygen species induced by [[5,10 (or 5,15)-bis(N-methyl-4-pyridyl)-15,20 (or 10,20) diphenyl]porphinato]iron (cis-FeMPy(2)P(2)P or trans-FeMPy(2)P(2)P) with SOD activity. The SOD activities of the cis-FeMPy(2)P(2)P and trans-FeMPy(2)P(2)P were measured using stopped-flow kinetic analysis. The cell viability of four cell lines treated with cis-Fe-porphyrin, trans-Fe-porphyrin, mitomycin c (MMC), or cisplatin was estimated by the alamar blue exclusion assay of the modified MTT method. The amount of cis-FeMPy(2)P(2)P and trans-FeMPy(2)P(2)P in the Walker 256 cultured for 24 h was 4.0 and 2.6 fmolcell(-1), respectively, indicating that the plasma membrane permeability of the Fe-porphyrins depended on their structure. Cis-FeMPy(2)P(2)P selectively killed Walker 256 and H-4-II-E as cancer cells but not FR and BRL-3A as normal cells and showed a significant cytotoxicity for the cancer cells compared with trans-FeMPy(2)P(2)P, MMC and cisplatin. We believe that cis-FeMPy(2)P(2)P as an SOD mimic converts intracellular O(2)(*-) to H(2)O(2) and that H(2)O(2) or *OH causes DNA damage and induces cell death. This result suggests that for the SOD mimic, O(2)(*-) may be useful as a target molecule to induce selective cell death between cancer and normal cells and that a metalloporphyrin having SOD activity is a new class of anticancer agents.     

SHIP2 controls PtdIns(3,4,5)P(3) levels and PKB activity in response to oxidative stress

Reactive oxygen species (ROS) are known to be involved in redox signalling pathways that may contribute to normal cell function as well as disease progression. The tumour suppressor PTEN and the inositol 5-phosphatase SHIP2 are critical enzymes in the control of PtdIns(3,4,5)P(3) level. It has been reported that oxidants, including those produced in cells such as macrophages, can activate downstream signalling via the inactivation of PTEN. The present study evaluates the potential impact of SHIP2 on phosphoinositides in cells exposed to sodium peroxide. We used a model of SHIP2 deficient mouse embryonic fibroblasts (MEFs) stimulated by H(2)O(2): at 15 min, PtdIns(3,4,5)P(3) was markedly increased in SHIP2 -/- cells as compared to +/+ cells. In contrast, no significant increase in PtdIns(3,4)P(2) could be detected at 15 or 120 min incubation of the cells with H(2)O(2) (0.6 mM). PKB activity was also upregulated in SHIP2 -/- cells as compared to +/+ cells in response to H(2)O(2). SHIP2 add back experiments in SHIP2 -/- cells confirm its critical role as a lipid phosphatase in the control of PtdIns(3,4,5)P(3) level in response to H(2)O(2). We conclude that SHIP2 lipid phosphatase activity plays an important role in the metabolism PtdIns(3,4,5)P(3) which is demonstrated in oxygen stressed cells.     

"Waste gas is not waste": advance in the research of hydrogen sulfide

The discovery of endogenous gasotransmitters puts forwards a new concept, "waste gas is not waste". Hydrogen sulfide (H(2)S) is considered as a new member of gasotransmitter family, following nitric oxide (NO) and carbon monoxide (CO). Recently, the understanding of H(2)S biological effect and its mechanisms has been deepened, especially the pathophysiological significance of H(2)S in the various diseases such as cardiovascular diseases, neurological diseases, respiratory diseases, endocrine diseases, etc. This article reviews recent progress of basic, clinical and pharmacological researches related to endogenous H(2)S, including the regulatory effects of H(2)S on the cell proliferation, apoptosis, inflammation, angiogenesis and ion channels, the role of endogenous H(2)S pathway in the pathogenesis of various diseases, as well as the study of the H(2)S donor and H(2)S-related drugs.     

Bis-intercalative binding to DNA of novel bis(10-methyl)acridinium chlorides and its dependence on chain length of linker.

The synthesis of a series of novel bis(10-methyl)acridinium compounds (both unsubstituted and the 6-chloro-2-methoxy substituted) linked by methylene bridges of lengths from (CH2)4 to (CH2)12 and in one case by spermine is described. Their ability to bind to duplex DNA was compared by their relative inhibition of E. coli DNA polymerase catalyzed DNA synthesis. It was determined that they function as DNA template inhibitors and do not affect the DNA polymerase directly. Their ability to function as bis-intercalators was assessed by a novel and convenient topoisomerase fluorescent assay. It was concluded that whereas the (CH2)4-linked compounds act only as monofunctional intercalators because of steric constraints the (CH2)6-, (CH2)8-, and (CH2)10-linked substituted bisacridinium compounds, as well as the (CH2)10- and (CH2)12- unsubstituted analogues, function as bis-intercalators with DNA.     

Protection of PC12 cells from hydrogen peroxide-induced cytotoxicity by salvianolic acid B, a new compound isolated from Radix Salviae miltiorrhizae

A number of studies indicate that reactive oxygen species (ROS) are involved in neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The neuroprotective effects of salvianolic acid B (SalB) from Radix Salviae miltiorrhizae (RSM) against hydrogen peroxide (H2O2)-induced rat pheochromocytoma line PC12 injury were evaluated in the present study. Vitamin E, a potent antioxidant, was employed as a positive control agent. Following exposure of cells to H2O2 (150 microM), a marked decrease in cell survival and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as increased levels of malondialdehyde (MDA) production and lactate dehydrogenase (LDH) release were observed. In parallel, H2O2 caused significant elevation in intracellular Ca2+ level and caspase-3 activity, and induced apoptotic death as determined by flow cytometric assay. However, pretreatment of the cells with SalB (0.1-10 microM) prior to H2O2 exposure blocked these H2O2-induced cellular events noticeably. Moreover, SalB exhibited significantly higher potency as compared to Vitamin E. The present findings indicated that SalB exerts neuroprotective effects against H2O2 toxicity, which might be of importance and contribute to its clinical efficacy for the treatment of neurodegenerative diseases.     

Relatively stable N-ligated [2Fe2S](2+) clusters with dipyrromethane capping ligands

[2Fe2S] clusters with terminal N-ligation (His, Arg) and unique functions are increasingly recognized in biological systems. In this work three new [2Fe2S] clusters 1-3 with different 1,1'-dipyrrolmethane derivatives as chelating terminal ligands have been prepared and fully characterized, including by X-ray crystallography: (NEt(4))(2)[L(2)Fe(2)(mu-S)(2)] with L=Me(2)C(C(4)H(3)N)(2) (1), Ph(2)C(C(4)H(3)N)(2) (2), (CH(2))(5)C(C(4)H(3)N)(2) (3). These systems represent rare examples of synthetic [2Fe2S] complexes with N-donor capping ligands. While geometric parameters as well as spectroscopic and electrochemical characteristics of the new complexes are as anticipated, the chelating nature of the terminal ligands in 1-3 imparts a relatively high stability that will be advantageous for reactivity studies of the [2Fe2S] core.     

Formation of Hydrogen and Formate by Ruminococcus albus

Radioisotopic growth studies with specifically labeled (14)C-glucose confirmed that Ruminococcus albus, strain 7, ferments glucose mainly by the Embden-Myerhof-Parnas pathway to acetate, ethanol, formate, CO(2), H(2), and an unidentified product. Cell suspensions and extracts converted pyruvate to acetate, H(2), CO(2), and a small amount of ethanol. Formate was not produced from pyruvate and was not degraded to H(2) and CO(2), indicating that formate was not an intermediate in the production of H(2) and CO(2) from pyruvate. Cell extract and (14)C-glucose growth studies showed that the H(2)-producing pyruvate lyase reaction is the major route of H(2) and CO(2) production. An active pyruvate-(14)CO(2) exchange reaction was demonstrable with cell extracts. The (14)C-glucose growth studies indicated that formate, as well as CO(2), arises from the 3 and 4 carbon positions of glucose. A formate-producing pyruvate lyase system was not demonstrable either by pyruvate-(14)C-formate exchange or by net formate formation from pyruvate. Growth studies with unlabeled glucose and labeled (14)CO(2) or (14)C-formate suggest that formate arises from the 3 and 4 carbon positions of glucose by an irreversible reduction of CO(2). The results of the studies on the time course of formate production showed that formate production is a late function of growth, and the rate of production, as well as the total amount produced, increases as the glucose concentration available to the organism increases.     

Elevated CO(2) levels cause mitochondrial dysfunction and impair cell proliferation

Elevated CO(2) concentrations (hypercapnia) occur in patients with severe lung diseases. Here, we provide evidence that high CO(2) levels decrease O(2) consumption and ATP production and impair cell proliferation independently of acidosis and hypoxia in fibroblasts (N12) and alveolar epithelial cells (A549). Cells exposed to elevated CO(2) died in galactose medium as well as when glucose-6-phosphate isomerase was knocked down, suggesting mitochondrial dysfunction. High CO(2) levels led to increased levels of microRNA-183 (miR-183), which in turn decreased expression of IDH2 (isocitrate dehydrogenase 2). The high CO(2)-induced decrease in cell proliferation was rescued by α-ketoglutarate and overexpression of IDH2, whereas proliferation decreased in normocapnic cells transfected with siRNA for IDH2. Also, overexpression of miR-183 decreased IDH2 (mRNA and protein) as well as cell proliferation under normocapnic conditions, whereas inhibition of miR-183 rescued the normal proliferation phenotype in cells exposed to elevated levels of CO(2). Accordingly, we provide evidence that high CO(2) induces miR-183, which down-regulates IDH2, thus impairing mitochondrial function and cell proliferation. These results are of relevance to patients with hypercapnia such as those with chronic obstructive pulmonary disease, asthma, cystic fibrosis, bronchopulmonary dysplasia, and muscular dystrophies.     

Therapeutic potential of the 2-alkyl and 2-alkylidene-19-nor-(20S)-modified analogs of 1alpha,25-dihydroxyvitamin D3

Five analogs of 19-nor-1alpha,25-dihydroxyvitamin D(3) are described that show highly selective and potent activities. The 2-methylene-19-nor-(20S)-1alpha25-dihydroxyvitamin D(3) (2MD) and its 2alpha-methyl sister are selectively active on the osteoblast. 2MD is bone anabolic and causes bone formation in vivo and in vitro and is being developed as a therapy for bone loss diseases such as osteoporosis. 2-Methylene-19-nor (20S)-bishomo-1alpha-hydroxypregnacalciferol (2BMP) has no activity on calcium in vivo while totally suppressing circulating parathyroid hormone. Its homologs, i.e. 2-methylene-19-nor-1alpha-hydroxy-homopregnacalciferol (2MP) and 2-methylene-19-nor-1alpha-hydroxypregnacalciferol (2MPC) act similarly but are either less selective (2MP) or not as potent (2MPC). These abbreviated side chain analogs will be developed for diseases where a rise in serum calcium is not desired, as for example, cancer, renal osteodystrophy, psoriasis and autoimmune diseases.