76203-93-5Relevant academic research and scientific papers
Additivity or cooperativity: Which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?
Nasief, Nader N.,Hangauer, David
, p. 897 - 915 (2015/05/27)
Predicting how binding affinity responds to ligand structural modifications in structure-activity relationship studies (SAR) is a major challenge in medicinal chemistry. This is particularly true when two or more of these modifications are carried out simultaneously. In this study, we present binding affinity data from several series of thermolysin inhibitors in which simultaneous structural modifications were investigated to determine whether they are cooperative or additive. Data revealed that, while additivity is at work in some cases, cooperativity is more commonly demonstrated. Cooperativity and additivity were then correlated with ligand descriptors, such as the spacing and the topological features of the modified groups, in a manner that may provide guidance as to when each model should be utilized. Cooperativity was particularly associated with contiguous groups and small unbranched hydrophobic side chain. Additivity, on the other hand, was associated with moderately distant hydrophobic group combinations and side chain branching. Such correlations can improve the predictability of SAR studies and can provide a starting point for additional investigations that may lead to further significant enhancements in the current scoring functions.
Influence of neighboring groups on the thermodynamics of hydrophobic binding: An added complex facet to the hydrophobic effect
Nasief, Nader N.,Hangauer, David
, p. 2315 - 2333 (2014/04/17)
The thermodynamic consequences of systematic modifications in a ligand side chain that binds in a shallow hydrophobic pocket, in the presence and absence of a neighboring ligand carboxylate group, were evaluated using isothermal titration calorimetry (ITC
Water mediated ligand functional group cooperativity: The contribution of a methyl group to binding affinity is enhanced by a COO- group through changes in the structure and thermodynamics of the hydration waters of ligand-thermolysin complexes
Nasief, Nader N.,Tan, Hongwei,Kong, Jing,Hangauer, David
, p. 8283 - 8302 (2013/01/15)
Ligand functional groups can modulate the contributions of one another to the ligand-protein binding thermodynamics, producing either positive or negative cooperativity. Data presented for four thermolysin phosphonamidate inhibitors demonstrate that the d
Intramolecular nucleophilic catalysis and the exceptional reactivity of N-benzyloxycarbonyl α-aminophosphonochloridates
Cullis, Paul M.,Harger, Martin J.P.
, p. 1538 - 1543 (2007/10/03)
The intramolecular nucleophilic catalysis and the exceptional reactivity of N-benzyloxycarbonyl α-aminophosphonochloridates were discussed. It was found that N-benzyloxycarbonyl derivatives of α-aminophosphonochloridates were highly reactive because of in
Reactive species formed from N-benzyloxycarbonyl α-aminophosphonochloridates and triethylamine: Probable identity and implications for synthesis
Cullis, Paul M.,Harger, Martin J. P.
, p. 458 - 459 (2007/10/03)
The sterically congested phosphonochloridate BnOCONHCMe2P(O)(OMe)Cl reacts rapidly with Et3N to give what is thought to be an oxazaphospholine oxide 7 (and Et3NHCl); unhindered BnOCONHCH2P(O)(OMe)Cl seems to rea
AN ANALYSIS OF THE ENZYME-INHIBITOR BINDING INTERACTIONS FOR PHOSPHONIC ACID TRANSITION STATE ANALOGS OF THERMOLYSIN
Bartlett, Paul A.,Marlowe, Charles K.
, p. 537 - 544 (2007/10/02)
Potent inhibitors of the zinc endopeptidase thermolysin are produced on replacement of the scissile peptide linkage with phosphonamidate or phosphonate ester moieties.These inhibitors have been shown to be transition state analogs, and a comparison betwee
AMINOPHOSPHONIC ACIDS. PART XVII. SYNTHESES AND PROPERTIES OF N-ACYL-1-AMINOALKANEPHOSPHONIC ACID 2-CYANOETHYL ESTERS
Szewczyk, Jerzy,Rachon, Janusz,Wasielewski, Czeslaw
, p. 477 - 483 (2007/10/02)
2-cyanoethyl monoesters and non-symmetrical 2-cyanoethyl-methyl diesters of N-acyl-1-amino-alkanephosphonic acid were prepared.Properties of 2-cyanoethyl esters as protecting groups of a phosphonic group were examined.
