16876-04-3Relevant articles and documents
Predicting the physicochemical profile of diastereoisomeric histidine-containing dipeptides by property space analysis
Vistoli, Giulio,Straniero, Valentina,Pedretti, Alessandro,Fumagalli, Laura,Bolchi, Cristiano,Pallavicini, Marco,Valoti, Ermanno,Testa, Bernard
experimental part, p. 566 - 576 (2012/08/29)
Objectives: This study aimed at measuring the lipophilicity and ionization constants of diastereoisomeric dipeptides, interpreting them in terms of conformational behavior, and developing statistical models to predict them. Methods: A series of 20 dipeptides of general structure NH2-L-X-(L or D)-His-OMe was designed and synthetized. Their experimental ionization constants (pK1, pK2 and pK3) and lipophilicity parameters (log PN and log D7.4) were measured by potentiometry. Molecular modeling in three media (vacuum, water, and chloroform) was used to explore and sample their conformational space, and for each stored conformer to calculate their radius of gyration, virtual log P (preferably written as log PMLP, meaning obtained by the molecular lipophilicity potential (MLP) method) and polar surface area (PSA). Means and ranges were calculated for these properties, as was their sensitivity (i.e., the ratio between property range and number of rotatable bonds). Results: Marked differences between diastereoisomers were seen in their experimental ionization constants and lipophilicity parameters. These differences are explained by molecular flexibility, configuration-dependent differences in intramolecular interactions, and accessibility of functional groups. Multiple linear equations correlated experimental lipophilicity parameters and ionization constants with PSA range and other calculated parameters. Conclusion: This study documents the differences in lipophilicity and ionization constants between diastereoisomeric dipeptides. Such configuration-dependent differences are shown to depend markedly on differences in conformational behavior and to be amenable to multiple linear regression.
Synthesis and Biological Activity of Angiotensin II Analogues Containing a Val-His Replacement, ValΨHis
Mohan, Raju,Chou, Yuo-Ling,Bihovsky, Ron,Lumma, William C.,Erhardt, Paul W.,Shaw, Kenneth J.
, p. 2402 - 2410 (2007/10/02)
The dipeptide mimic ValΨHis (4) was incorporated into angiotensin II (AII) analogues to provide an octapeptide saralisn derivative (29) as well as tetrapeptide analogue 19.Three C-terminal tetrapeptides (21, 25, and 28) were also prepared.All
