title: Universal peptidomimetics.
abstract: This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.
authors.affiliation: Department of Chemistry and Laboratory for Molecular Simulation, Texas A&M University, Box 30012, College Station, Texas 77842, United States.
authors.forename: Eunhwa
authors.initials: E
authors.lastname: Ko
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Perez
authors.forename: Genliang
authors.initials: G
authors.lastname: Lu
authors.forename: Amber
authors.initials: A
authors.lastname: Schaefer
authors.forename: Kevin
authors.initials: K
authors.lastname: Burgess
mesh_terms: D007700:Kinetics; D008958:Models, Molecular; D057786:Peptidomimetics; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D057786:Peptidomimetics