title: Contemporary strategies for the stabilization of peptides in the alpha-helical conformation.
abstract: Herein we review contemporary synthetic and protein design strategies to stabilize the alpha-helical motif in short peptides and miniature proteins. Advances in organometallic catalyst design, specifically for the olefin metathesis reaction, enable the use of hydrocarbon bridges to either crosslink side chains of specific residues or mimic intramolecular hydrogen bonds with carbon-carbon bonds. The resulting hydrocarbon-stapled and hydrogen bond surrogate alpha-helices provide unique synthetic ligands for targeting biomolecules. In the protein design realm, several classes of miniature proteins that display stable helical domains have been engineered and manipulated with powerful in vitro selection technologies to yield libraries of sequences that retain their helical folds. Rational re-design of these scaffolds provide distinctive reagents for the modulation of protein-protein interactions.
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Henchey
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Jochim
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Arora
mesh_terms: D000818:Animals; D003432:Cross-Linking Reagents / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D055550:Protein Stability; D017433:Protein Structure, Secondary
chemical_list: D003432:Cross-Linking Reagents; D010455:Peptides
references.citation: J Am Chem Soc. 2008 Mar 12;130(10):2948-9
references.pmid: 18271592
references.citation: J Am Chem Soc. 2007 Mar 7;129(9):2456-7
references.pmid: 17284038
references.citation: J Am Chem Soc. 2006 Oct 11;128(40):13284-9
references.pmid: 17017810
references.citation: Chem Rev. 2001 Dec;101(12):3893-4012
references.pmid: 11740924
references.citation: J Am Chem Soc. 2006 Mar 22;128(11):3496-7
references.pmid: 16536504
references.citation: J Am Chem Soc. 2003 Nov 26;125(47):14336-47
references.pmid: 14624582
references.citation: Int J Pept Protein Res. 1988 Dec;32(6):441-54
references.pmid: 3149952
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):13-20
references.pmid: 8552589
references.citation: Biopolymers. 2007;88(5):657-86
references.pmid: 17427181
references.citation: Angew Chem Int Ed Engl. 1998 Dec 17;37(23):3281-3284
references.pmid: 29711420
references.citation: Nat Chem Biol. 2007 May;3(5):252-62
references.pmid: 17438550
references.citation: Nat Struct Biol. 2002 Jun;9(6):425-30
references.pmid: 11979279
references.citation: Bioinformatics. 2007 Aug 1;23(15):1909-18
references.pmid: 17510165
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13426-30
references.pmid: 9391041
references.citation: Angew Chem Int Ed Engl. 2008;47(10):1879-82
references.pmid: 18224636
references.citation: J Am Chem Soc. 2003 Nov 5;125(44):13525-30
references.pmid: 14583049
references.citation: J Am Chem Soc. 2006 Jul 19;128(28):9248-56
references.pmid: 16834399
references.citation: Chem Soc Rev. 2007 Feb;36(2):326-34
references.pmid: 17264933
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11273-8
references.pmid: 13679575
references.citation: Chem Commun (Camb). 2005 May 28;(20):2552-4
references.pmid: 15900323
references.citation: Org Biomol Chem. 2006 Nov 21;4(22):4074-81
references.pmid: 17312961
references.citation: J Am Chem Soc. 2004 Apr 21;126(15):4828-42
references.pmid: 15080687
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14664-9
references.pmid: 12417739
references.citation: Chemistry. 2008;14(3):857-63
references.pmid: 17969217
references.citation: Nat Biotechnol. 2005 Oct;23(10):1257-68
references.pmid: 16211069
references.citation: Chem Rev. 2005 Mar;105(3):973-99
references.pmid: 15755082
references.citation: J Am Chem Soc. 2001 Mar 28;123(12):2929-30
references.pmid: 11456999
references.citation: J Am Chem Soc. 2007 Nov 21;129(46):14154-5
references.pmid: 17960932
references.citation: J Biol Chem. 2007 Mar 30;282(13):9813-9824
references.pmid: 17264074
references.citation: Science. 2004 Sep 3;305(5689):1466-70
references.pmid: 15353804
references.citation: Curr Opin Struct Biol. 2007 Aug;17(4):481-7
references.pmid: 17870470
references.citation: Biopolymers. 2002;66(1):49-75
references.pmid: 12228920
references.citation: Angew Chem Int Ed Engl. 2005 Oct 14;44(40):6525-9
references.pmid: 16172999
references.citation: J Am Chem Soc. 2008 Apr 2;130(13):4334-7
references.pmid: 18331030
references.citation: J Am Chem Soc. 2003 Jun 11;125(23):6852-3
references.pmid: 12783522
references.citation: J Mol Biol. 2008 May 2;378(3):565-80
references.pmid: 18374356
references.citation: Chem Rev. 2001 Oct;101(10):3219-32
references.pmid: 11710070
references.citation: J Mol Biol. 1988 Jun 5;201(3):601-19
references.pmid: 3418712
references.citation: Org Biomol Chem. 2007 Nov 21;5(22):3577-85
references.pmid: 17971985