Analogues of arginine vasopressin modified in position 2 and 3 with conformationally constrained dipeptide fragments. |
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Authors: | El bieta empicka,Izabela Derdowska,Wioleta Kowalczyk,Olga Dawidowska,Adam Prahl,Marcin Janecki,Tomasz Jasi ski,Henryk I. Trzeciak,Bernard Lammek |
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Affiliation: | Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. |
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Abstract: | 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 -Phe-Phe and D-Phe-D-Phe, dipeptides having a -CH2-CH2- link bridging two nitrogens. All the new peptides were tested for vasopressor and antidiuretic activities. Four peptides with pA2 values ranging from 5.96 to 7.21 turned out to be weak or moderately potent V1a 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. |
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Keywords: | analogues of arginine vasopressin (AVP) antivasopressor activity conformational constraints |
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