title: Protease-resistant peptide design-empowering nature's fragile warriors against HIV.
abstract: Peptides have great potential as therapeutic agents, but their use is often limited by susceptibility to proteolysis and their resulting in vivo fragility. In this review, we focus on peptidomimetic approaches to produce protease-resistant peptides with the potential for greatly improved clinical utility. We focus on the use of mirror-image (D-peptide) and ß-peptides as two leading approaches with distinct design principles and challenges. Application to the important and difficult problem of inhibiting HIV entry illustrates the current state-of-the-art in peptidomimetic technologies. We also summarize future directions for this field and highlight remaining obstacles to widespread use of protease-resistant peptides.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Weinstock
authors.forename: J Nicholas
authors.initials: JN
authors.lastname: Francis
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Redman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kay
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D015195:Drug Design; D006678:HIV; D015700:HIV Envelope Protein gp41 / Q000737:chemistry; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000596:Amino Acids; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D019151:Peptide Library; D010455:Peptides; D057786:Peptidomimetics; D010447:Peptide Hydrolases