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dc.contributor.advisorMartin, Stephen F.en
dc.creatorAu, Vincenten
dc.date.accessioned2012-05-18T21:10:41Zen
dc.date.available2012-05-18T21:10:41Zen
dc.date.issued2012-05en
dc.identifier.urihttp://hdl.handle.net/2152/15660en
dc.description.abstractPreorganizing a flexible ligand in the shape it adopts when bound to a protein should theoretically result in an increased binding affinity due to a smaller entropic penalty during binding. Previous work, however, shows that this is not always the case. Constraining the pY residue of a short peptidic sequence, pYEEl, that binds to the Src Homology 2 domain of the Src kinase (Src SH2 domain) resulted in an entropic advantage, but this was offset by an enthalpic penalty that resulted in approximately equal binding affinities of the flexible and constrained ligands. Based on NMR relaxation and molecular dynamics studies of the complex, it is hypothesized that suboptimal interactions within the pY binding site ("binding hot spot") may be the reason for the loss of enthalpy. In order to test this hypothesis, a cyclopropane-derived replacement for the isoleucine residue, which binds to a hydrophobic site of the domain, and its succinate-derived flexible analog are being synthesized. This paper reports the synthesis progress towards the flexible analog.en
dc.language.isoengen
dc.subjectSrc SH2en
dc.subjectpeptideen
dc.subjectCollege of Natural Sciencesen
dc.titleProgress towards the synthesis of succinate-derived flexible peptide for the Src SH2 domainen
dc.typeThesisen
dc.description.departmentChemistryen
dc.description.departmentBiochemistryen


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