New analogues of bradykinin containing a conformationally restricted dipeptide fragment in their molecules

: The present paper describes the synthesis and some pharmacological properties of two new bradykinin analogues containing the ethylene‐bridged dipeptide Phe‐Phe in their molecules. In a further two peptides this modification was combined with acylation of the N‐terminus with 1‐adamantaneacetic acid...

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Bibliographic Details
Published in:The journal of peptide research 2001-01, Vol.57 (1), p.11-18
Main Authors: Derdowska, I., Prahl, A., Lammek, B., Neubert, K., Hartrodt, B., Kania, A., Dobrowolski, D., Malhem, S., Trzeciak, H.I., Wierzbad, T.
Format: Article
Language:English
Subjects:
Acetic Acid - chemistry
Adamantane - analogs & derivatives
Adamantane - chemical synthesis
Adamantane - pharmacology
Amino Acid Sequence
Amino Acids - chemistry
Animals
B2-antagonists
Blood Pressure - drug effects
bradykinin
Bradykinin - analogs & derivatives
Bradykinin - chemical synthesis
Bradykinin - pharmacology
Female
Male
Molecular Sequence Data
Peptides - chemistry
Phenylalanine - chemistry
Protein Conformation
Rats
Rats, Wistar
sterically restricted fragment
Uterus - drug effects
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Summary:: The present paper describes the synthesis and some pharmacological properties of two new bradykinin analogues containing the ethylene‐bridged dipeptide Phe‐Phe in their molecules. In a further two peptides this modification was combined with acylation of the N‐terminus with 1‐adamantaneacetic acid. Finally, we synthesized four analogues by removing the Ser6 residue from the four peptides mentioned above. The activity of the new analogues was assayed on isolated rat uterus (RUT) and in rat blood pressure tests (BPT). The results clearly indicate that the proposed modification, alone or in combination with other changes, resulted in either a drop in antiuterotonic activity or even in conversion to an agonism. Although this tendency is not so distinct in blood pressure assays, the antagonistic potency of the new analogues is also diminished. Nevertheless, it was demonstrated that the d‐amino acid in position 7 which, until recently, was considered necessary for antagonism, may be replaced, together with the amino acid occupying position 8, by a suitable, sterically restricted L,L‐dipeptide unit.
ISSN:1397-002X
1399-3011
DOI:10.1034/j.1399-3011.2001.00811.x