Cyclic analogues of bradykinin

Mutulis, Felikss; Chipens, G. I.; Mutule, Ilze; Maurops, G.

doi:10.1111/j.1399-3011.1985.tb01012.x

Cited by 5 publications

(2 citation statements)

References 6 publications

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“…The cyclo-KL (XI) was purified and characterized as indicated for cyclo-BK. Cyclo BK and KL analogues were previously described and their biological properties and conformational features extensively investigated (10)(11)(12)(13)(14)(15).…”

Section: Synthesis Of Cyclo-bkmentioning

confidence: 99%

Synthesis and biological activity of some linear and cyclic kinin analogues

Gobbo

Biondi

Filira

et al. 1994

International Journal of Peptide and Protein Research

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Syntheses are described of some linear and cyclic kinin analogues. Cyclization, by the diphenyl‐phosphorazide method, of linear peptides prepared by the solid‐phase procedure based on Fmoc chemistry, was used for preparing cyclo‐bradykinin and cyclo‐kallidin (cyclo‐Lys‐bradykinin). Removal of the protecting group from the lysine side chain of cyclo‐kallidin followed by acylation with the N‐terminal sequence of vespulakinin 1 (VSK l), Fmoc‐Thr(tBu)‐Ala‐Thr(tBu)‐Thr(tBu)‐Arg(Pmc)‐Arg(Pmc)‐Arg(Pmc)‐Gly‐OH, by the Bop‐HOBt procedure, yielded the protected Nε‐(1‐8 VSK 1)‐cyclo‐Nα‐kallidin, which was deblocked by acid treatment and purified by semi‐preparative HPLC. The diglycosylated 1‐8 VSK 1 sequence Boc‐Thr(tBu)‐Ala‐ (Galβ)Thr‐(Galβ)Thr‐Arg(Pmc)‐Arg(Pmc)‐Arg(Pmc)‐Gly‐OH was also synthesized by the solid‐phase procedure and used to prepare the Nε‐[(Galβ)Thr3, (Galβ)Thr3, 1‐8 VSK 1]‐cyclo‐Nα‐kallidin. Peptides and glycopeptides were characterized by amino acid analysis, optical rotation, analytical HPLC and FAB‐MS. Preliminary pharmacological experiments showed that the cyclic kinin analogues are much less potent than bradykinin but still show specific bradykinin‐like actions that support the hypothesis of the presence of a pharmacophore in the centre of the (brady)kinin molecule.

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Section: Synthesis Of Cyclo-bkmentioning

confidence: 99%

Synthesis and biological activity of some linear and cyclic kinin analogues

Gobbo

Biondi

Filira

et al. 1994

International Journal of Peptide and Protein Research

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“…In the last two decades about 30 analogues with different types of cyclization were synthesized in various laboratories. The first compounds were obtained by the peptide group in Riga (35)(36)(37)(38) by cyclization between N-terminus and C-terminus in bradykinin agonists. Most of these compounds have moderate activity on RUT and reduce blood pressure.…”

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confidence: 99%

New cyclic bradykinin antagonists containing disulfide and lactam bridges at the N‐terminal sequence*

Seyfarth

Castro

Liepina

et al. 1995

International Journal of Peptide and Protein Research

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Continuing our studies of the bioactive conformation of bradykinin (BK) antagonists, we synthesized a first series of analogues with side-chain cyclization in the N-terminal sequence. Through this conformational constraint it should be possible to gain insight into their three-dimensional structure. The cycles were proposed on the basis of existing ideas and hypotheses about the receptor bound conformation of BK and its antagonists. The reported peptides contain D-Phe at position 7 or D-Tic-Oic (~-tetrahydroisoquinoline-3carboxyl-octahydroindole-2-carboxylic acid) at positions 7 and 8, respectively, and a disulfide or lactam bridge between positions 0 and 6 . Syntheses, including cyclization reactions, were carried out on PAM resin. The biological activity of the lead compound [~phe']-BK, the linear precursors and the cyclic peptides, as estimated on isolated rat uterus, guinea pig ileum and lung strips, are in the same range. The conformational properties of the new cyclic analogues were studied through energy minimization on a model compound. The results of the calculations support the existence of low-energy structures containing a 8-turn. Therefore, such a turn in the N-terminal segment of the molecule can be proposed as an important structural feature of the bioactive conformation of BK antagonists. 0 Munksgaard 1995.

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