title: Rapid probing of biological surfaces with a sparse-matrix peptide library.
abstract: Finding unique peptides to target specific biological surfaces is crucial to basic research and technology development, though methods based on biological arrays or large libraries limit the speed and ease with which these necessary compounds can be found. We reasoned that because biological surfaces, such as cell surfaces, mineralized tissues, and various extracellular matrices have unique molecular compositions, they present unique physicochemical signatures to the surrounding medium which could be probed by peptides with appropriately corresponding physicochemical properties. To test this hypothesis, a naïve pilot library of 36 peptides, varying in their hydrophobicity and charge, was arranged in a two-dimensional matrix and screened against various biological surfaces. While the number of peptides in the matrix library was very small, we obtained "hits" against all biological surfaces probed. Sequence refinement of the "hits" led to peptides with markedly higher specificity and binding activity against screened biological surfaces. Genetic studies revealed that peptide binding to bacteria was mediated, at least in some cases, by specific cell-surface molecules, while examination of human tooth sections showed that this method can be used to derive peptides with highly specific binding to human tissue.
authors.affiliation: C3 Jian, Inc., Inglewood, California, United States of America.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Yarbrough
authors.forename: Randal
authors.initials: R
authors.lastname: Eckert
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hagerman
authors.forename: Fengxia
authors.initials: F
authors.lastname: Qi
authors.forename: Renate
authors.initials: R
authors.lastname: Lux
authors.forename: Ben
authors.initials: B
authors.lastname: Wu
authors.forename: Maxwell H
authors.initials: MH
authors.lastname: Anderson
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002176:Candida albicans / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003743:Dental Enamel / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D016941:Myxococcus xanthus / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000378:metabolism; D013499:Surface Properties; D014070:Tooth / Q000737:chemistry / Q000378:metabolism
chemical_list: D019151:Peptide Library; D010455:Peptides