Hydrocarbon-Stapled Peptides – Custom Synthesis & Reagents


The innovative technique of hydrocarbon stapling in peptides is introducing valuable new functionality to peptide-related research. AnaSpec is pleased to offer custom synthesis of hydrocarbon-stapled peptides.

Hydrocarbon-stapled peptides are peptides capable of forming stable alpha helical structure as a result of "hydrocarbon stapling."1,2 Many biological pathways, such as signal transduction, occur because of intracellular protein-protein interactions, which frequently are mediated by the α-helix structures of proteins. However, the use of short protein fragments (peptides) leads to a loss of secondary structure, which makes them susceptible to proteolysis and impermeable across cell membrane.1 Verdine's group has shown that these problems could be overcome by a chemical modification of an alpha-helical peptide they termed hydrocarbon-stapled peptide.1,2 The modified hydrocarbon-stapled peptide is helical, relatively protease resistant, cell-permeable and binds with increased binding affinity to its target. Hydrocarbon stapling may provide a useful strategy in researching experimental and therapeutic modulation of protein-protein interactions as well as in in vivo pharmacokinetics studies.



Figure 1.
Strategy for hydrocarbon-stapled peptide with enhanced α-helical structure.

In addition to offering stapled peptides [(i and i+4) and (i and i+7)] custom synthesis service, AnaSpec is very pleased to offer Fmoc amino acids for use in synthesizing stapled peptides (Table 1); as well as three GO™ (catalog) stapled peptides (Table 2).

To view a paper from the Journal of Molecular Biology entitled "A Cell-penetrating Helical Peptide as a Potential HIV-1 Inhibitor," reported by scientists from the Lindsley F. Kimball Research Institute of the New York Blood Center, New York Structural Biology, AnaSpec, Inc. and the National Cancer Institute-Frederick, please click here.

AnaSpec presented a poster on hydrocarbon-stapled peptides at the 20th American Peptide Society. Click here to download the PDF

Table 1. Fmoc amino acids for the synthesis of stapled peptides.

Product

Size

Catalog #

(R)-N-Fmoc-2-(2'-propenyl) alanine

100 mg
500 mg
1 g
5 g
10 g

 

64171-100
64171-500
64171-1000
64171-5000
64171-10000

 

(S)-N-Fmoc-2-(2'-propenyl) alanine

100 mg
500 mg
1 g
5 g
10 g

64170-100
64170-500
64170-1000
64170-5000
64170-10000

(R)-N-Fmoc-2-(4'-pentenyl) alanine

100 mg
500 mg
1 g
5 g
10 g

64173-100
64173-500
64173-1000
64173-5000
64173-10000

(S)-N-Fmoc-2-(4'-pentenyl) alanine

100 mg
500 mg
1 g
5 g
10 g

64172-100
64172-500
64172-1000
64172-5000
64172-10000

(R)-N-Fmoc-2-(7'-octenyl) alanine

100 mg
500 mg
1 g
5 g
10 g

64175-100
64175-500
64175-1000
64175-5000
64175-10000

(S)-N-Fmoc-2-(7'-octenyl) alanine

100 mg
500 mg
1 g
5 g
10 g

64174-100
64174-500
64174-1000
64174-5000
64174-10000

Fmoc-2,2-Bis(4'-pentenyl) glycine (B5)
2-(((9H-Fluoren-9-yl) methoxy) carbonylamino)-2-(pent-4-enyl)hept-6- enoic acid (B5)

100 mg
500 mg
1 g
5 g
10 g

64177-100
64177-100
64177-1000
64177-5000
64177-10000

 

Table 2. Listing of GO™ (catalog) stapled peptides.

Hydrocarbon-Stapled Helix SAHBA Peptide
"EDIIRNIARHLAXVGDX-Nle-DRSIW (with special cyclization to get double bond, X= (S)-2-(2'pentenyl)alanine)"

1 mg

5 mg

63735-1

63735-5

NYAD-1
"ITFXDLLXYYGP-NH2 (with special cyclization to get double bond, X= (S)-alpha-(2'-pentenyl)alanine)"

1 mg

5 mg

63734-1

63734-5

FITC-beta-Ala-NYAD-1 (NYAD-2)
"FITC-(beta-A)-ITFXDLLXYYGP-NH2 (with special cyclization to get double bond, X= (S)-alpha-(2'-pentenyl)alanine)"

0.25 mg

63733-025

References:
1. Walensky, LD. et al. Science 305, 1466 (2004).
2. Schafmeister, CE. et al. J. Am. Chem. Soc. 122, 5891 (2000).
3. Zhang, HT. et al. J. Mol. Biol. 378(3), 565-580 (2008).