98435-76-8Relevant articles and documents
EPHA4 CYCLIC PEPTIDE ANTAGONISTS AND METHODS OF USE THEREOF
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Paragraph 0653-0654; 0656, (2019/11/19)
Disclosed herein are compounds and methods of use thereof for the modulation of EphA4 receptor activity. In an aspect, is provided a method of treating or preventing a disease or disorder mediated by EphA4, comprising administering to a subject in need thereof a therapeutically effective amount of a compound as described herein, including certain embodiments, or the structural Formula (I), (l-A), (II), (III), (IV), (IV-1), (V), (Vl-A), (Vl-B), (VII-1), (VII-2), (VIII-1), or (VIII-2), or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
N-ALKYLATED AMINO ACIDS AND OLIGOPEPTIDES, USES THEREOF AND METHODS FOR PROVIDING THEM.
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Page/Page column 17-19; 22-25, (2018/10/25)
The invention relates to the synthesis of amphiphilic amino acid derivatives, in particular to a method for the N-alkylation of an unprotected amino acid or the N-terminus of an oligopeptide substrate, comprising reacting said unprotected amino acid or oligopeptide substrate with an alcohol, e.g. a fatty alcohol, in the presence of a homogeneous transition metal catalyst.
Modulating hydrogen-bond basicity within the context of protein-ligand binding: A case study with thrombin inhibitors that?reveals a dominating role for desolvation
Nasief, Nader N.,Said, Ahmed M.,Hangauer, David
, p. 975 - 991 (2016/11/11)
Understanding subtle aspects of hydrogen bonding is a challenging but crucial task to improve our ability to design ligands with high affinity for protein hosts. To gain a deeper understanding of these aspects, we investigated a series of thrombin inhibitors in which the basicity of the ligand's group that accepts an H-bond from Gly216 was modulated via bioisosterism; e.g., a C=O acceptor was made electron deficient or rich via bioisosteric replacements of the adjacent moiety. Although the ligand's binding affinity was anticipated to improve when the H-bond basicity is increased (due to stronger H-bonding with the protein), we herein present data that unexpectedly revealed an opposite trend. This trend was attributed to a dominating role played by desolvation in determining the relative binding affinity. For example, a decrease in the H-bond basicity reduces the desolvation penalty and, as experimentally observed, improves the binding affinity, given that the reduction in the desolvation penalty dominates the change in the net contribution of the ligand's interactions with the protein. The current study, therefore, reveals that desolvation can be a major underlying cause for the apparently counterintuitive structure-activity relationship (SAR) outcomes, and indicates that understanding this factor can improve our ability to predict binding affinity and to design more potent ligands.