Synthesis and some biological activities of analogues of deamino-vasopressin with the disulphide bridge altered to a thioether bridge

Jošt, Karel; Procházka, Ž.; Cort, J. H.; Barth, Tomislav; Škopková, Jana; Prusík, Z.; Šorm, F.

doi:10.1135/cccc19742835

Cited by 30 publications

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“…1) while only dCDAVP is protected against A, C and D cleavage. Since dCDAVP has a sterically altered C-terminal tripeptide its smooth muscle activity is minimal and its extremely high antidiuretic activity (19) will be discussed in detail elsewhere (12). dCCAVP, protected against A and D cleavage, has possibly sufficient steric distortion of the cyclic port-ion of the molecule (18) that vasoconstrictor potency is reduced, but what activity it does exhibit is prolongedits antidiuretic activity, however, is higher than that of dAVP ( 1 2 , 18).…”

Section: Discussionmentioning

confidence: 99%

“…Materials. One of us (JLM) supplied lysine-vasopressin (LVP) , desamino-D-arginine8-vasopressin (dDAVP) (5 I ) , Na-glycyl,-glycyl-glycyl-lysine-vaso- (19). Prof. R.…”

Section: Methodsmentioning

confidence: 99%

“…The DValLVP extended-chain analogue is not included in the graphs because at doses up to 50 pg/kg we could not measure any significant regional haemodynamic response with this analogue ( Table 2 ) . The effect of "carba" alterations in the VP ring The pressor activity of dCAVP has been found to be about 30 9. less than that of LVP (19). Antidiuretic activity, on the other hand, was much higher than that of the natural vasopressins, and in the analogous case of oxytocin, mono-carba modifications were all associated with higher uterotonic potencies in comparison with the parent molecule ( 4 , 5 ) .…”

Section: Extended Chain Analoguesmentioning

confidence: 99%

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Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity

Cort

Albrecht

Nováková

et al. 1975

Eur J Clin Investigation

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Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbC1. The haemodynamic responses were measured at various time intervals up to 2 h after single I.V. injections of lysine-vasopressin and the followin8 of its analogues: a) with extended peptide chains at the N-terminal (including "hormonogens") N -glycyl-glycyl-glycyl-lysine-vasopressin, Na-glycyl-glycyl-glycyl-arginine-vasopressin and N -D-va lyl-1 y s ine-vas o pr e s s in, b) I' carba" mod if i ca t ions de s amino-c ar baar g in ine-vas o p r e s s in, desamho-carba6-D-arginine8-vasopressin, desamino-carba6-ornithine8-vasopressin, desamino-dicarbaarginine-vasopressin and c) other steric alterationsdesamino-D-arginine8-vasopressin and desamino-N-methylarginine8-vasopressin. Sub-pressor doses of lysine-vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 6 0 min. The presence of steric alterations in the C-terminal tripeptide of the molecule-D-arginine or N-methylarginine in sequence position 8practically completely eliminated vascular activity. The same was true for N -D-valyl-lysine-vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine-vasopressin. The two hormonogens (triglycyl N-terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of lysine-vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine-vasopressin, and was only starting to return to baseline values at the same time with the arginine-vasopressin hormonogen. The vascular potency of both mono-carba L-analogues was higher than that of lysine-vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the -S-s-, -SCH2 and -CHzCH2-bridges in the above analogues are not directly bound in the peptide-receptor complex and congtihte the limiting factor determining complex duration, or persistence of the active peptide in the "receptor compartment". These results provide an experimental basis for possible clinical application of triglycyl-vasopressin and carba-vasopressin in bleeding from both gut and utezus and for induction of menstruation.

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Section: Discussionmentioning

confidence: 99%

“…Materials. One of us (JLM) supplied lysine-vasopressin (LVP) , desamino-D-arginine8-vasopressin (dDAVP) (5 I ) , Na-glycyl,-glycyl-glycyl-lysine-vaso- (19). Prof. R.…”

Section: Methodsmentioning

confidence: 99%

Section: Extended Chain Analoguesmentioning

confidence: 99%

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Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity

Cort

Albrecht

Nováková

et al. 1975

Eur J Clin Investigation

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“…After an acidic pH of the solution was verified, the crude product was extracted with DCM (3Â50 mL). The organic extracts are combined, dried over anhydrous MgSO 4 and evaporated under reduced pressure to yield the crude product as a colourless viscous liquid that appears to be practically pure by analytical methods (4.15 g, 97% (12). The trichloroacetimidate reagent 11 (4.02 g, 14.4 mmol) was added to a solution of the carboxylic acid 10 (3.500 g, 11.04 mmol) in DCM (50 mL).…”

Section: N-((allyloxy)carbonyl)-o-(tert-butyldimethylsilyl)-d-homosermentioning

confidence: 99%

“…9 Although a number of replacements of the disulfide bridge are known in literature, replacement of the eSeSe linkage with the eCH 2 eSe (cystathionine, Cth, bridge) offers the advantage that it involves modification at just one atom, resulting in minimal structural perturbation and overcoming the reductive susceptibility of the peptide. 10 Several studies have described the results of replacing the eSeSe linkage with a Cth bridge in oxytocin, 11 vasopressin, 12 anti-cardiolipin antibody binders, 13 VCAM/VLA-4 antagonists 14 and analogues of compstatin. 15 Our group has been involved in the development of cyclic peptides as inhibitors of SPSB2 at the SPSB2-iNOS binding site.…”

Section: Introductionmentioning

confidence: 98%

An alternative approach to the synthesis of peptides containing a cystathionine bridge

Harjani¹,

Yap²,

Norton³

et al. 2016

Tetrahedron

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Understanding base‐assisted desulfurization using a variety of disulfide‐bridged peptides

2003

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A recently rediscovered reaction of base-assisted lanthionine formation has been applied to several systems of disulfide-bridged peptides. In addition to previously described nonapeptides consisting of i, i+3 cystine linkages, the reaction has now been extended to systems consisting of shorter (i, i+2) and longer (i, i+4) disulfide bridges. The desulfurization reaction is also compatible with disulfide bridges formed through homocysteines and penicillamines, yielding unusual amino acids such as cystathionine and beta,beta-dimethyl lanthionine (referred to as "penthionine") in a peptide chain, respectively. Systematic study of this transformation has provided several new insights into its mechanism. We have observed formation of dehydroalanine and dehydrovaline residues resulting from i, i+2-bridged cysteines and i, i+3-bridged cysteine/penicillamine peptides, respectively, thereby supporting a beta-elimination/Michael-addition mechanism for this transformation. Amino acid analysis and NMR data from total correlation spectroscopy (TOCSY) and (1)H-(13)C heteronuclear single quantum correlation (HSQC) experiments show three diastereomeric lanthionine-bridged peptides in the product mixture. But in the case of desulfurization of a cysteine/homocysteine containing disulfide-bridged peptide, Michael addition appears to be stereoselective, yielding a single stereoisomer of cystathionine within the peptide. According to molecular modeling and CD spectroscopy, constrained peptides such as those containing penicillamine are less likely to undergo facile desulfurization. Flexibility of the torsional angles (C(alpha)H-C(alpha)-C(beta)-S) corresponding to the cysteine residues and temperature appear to be contributing factors determining the extent of desulfurization.

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Synthesis and some biological activities of analogues of deamino-vasopressin with the disulphide bridge altered to a thioether bridge

Cited by 30 publications

References 0 publications

Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity

Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity

An alternative approach to the synthesis of peptides containing a cystathionine bridge

Understanding base‐assisted desulfurization using a variety of disulfide‐bridged peptides

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