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Analogues of arginine vasopressin modified in position 2 and 3 with conformationally constrained dipeptide fragments
Author(s) -
Łempicka Elżbieta,
Derdowska Izabela,
Kowalczyk Wioleta,
Dawidowska Olga,
Prahl Adam,
Janecki Marcin,
Jasiński Tomasz,
Trzeciak Henryk I.,
Lammek Bernard
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.600
Subject(s) - dipeptide , arginine , chemistry , peptide , stereochemistry , vasopressin , molecule , amino acid , amino acid residue , crystallography , peptide sequence , biochemistry , biology , organic chemistry , gene , genetics
This study describes the synthesis and some pharmacological properties of ten new analogues of arginine vasopressin (AVP) containing a conformationally constrained dipeptide fragment in the N ‐terminal part of their molecules. Amino acid residues in positions 2 and 3 of AVP and some of its agonistic analogues were replaced with $\newbox\sprulebox \newdimen\sprulewd \def\sprule#1#2{ \global\setbox\sprulebox=\hbox{#1} \sprulewd=\wd\sprulebox\advance \sprulewd by -2pt \matrix{\smash{\lower.67pc\hbox{#1}}\cr \vrule height #2pt\hbox to \sprulewd{\hrulefill}\vrule height #2pt\cr} } \sprule{-Phe-}{7}$ Phe and D $\newbox\sprulebox \newdimen\sprulewd \def\sprule#1#2{ \global\setbox\sprulebox=\hbox{#1} \sprulewd=\wd\sprulebox\advance \sprulewd by -2pt \matrix{\smash{\lower.67pc\hbox{#1}}\cr \vrule height #2pt\hbox to \sprulewd{\hrulefill}\vrule height #2pt\cr} } \sprule{-Phe-}{7}$ D ‐Phe, dipeptides having a CH 2 CH 2 link bridging two nitrogens. All the new peptides were tested for vasopressor and antidiuretic activities. Four peptides with pA 2 values ranging from 5.96 to 7.21 turned out to be weak or moderately potent V 1a antagonists. The results supplied new information about the structure—activity relationship of AVP analogues. As some of these were unexpected, they point to the need for caution when extrapolating previously known effects of modifications to analogues having conformationally constrained fragments in their molecules. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.