Evaluation of geranylazide and farnesylazide diphosphate for incorporation of prenylazides into a CAAX box-containing peptide using protein farnesyltransferase

:  Protein farnesyltransferase (PFTase) catalyzes the attachment of a geranylazide (C10) or farnesylazide (C15) moiety from the corresponding prenyldiphosphates to a model peptide substrate, N‐dansyl‐Gly‐Cys‐Val‐Ile‐Ala‐OH. The rates of incorporation for these two substrate analogs are comparable an...

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Bibliographic Details
Published in:The journal of peptide research 2005-06, Vol.65 (6), p.529-537
Main Authors: Rose, M.W., Rose, N.D., Boggs, J., Lenevich, S., Xu, J., Barany, G., Distefano, M.D.
Format: Article
Language:English
Subjects:
Alkyl and Aryl Transferases - metabolism
Azides - chemistry
CAAX box
cysteine modification
Diphosphates - chemical synthesis
farnesylazide
farnesyltransferase
geranylazide
peptide modification
Peptides - chemical synthesis
prenylated peptides
prenylazide
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Summary::  Protein farnesyltransferase (PFTase) catalyzes the attachment of a geranylazide (C10) or farnesylazide (C15) moiety from the corresponding prenyldiphosphates to a model peptide substrate, N‐dansyl‐Gly‐Cys‐Val‐Ile‐Ala‐OH. The rates of incorporation for these two substrate analogs are comparable and approximately twofold lower than that using the natural substrate farnesyl diphosphate (FPP). Reaction of N‐dansyl‐Gly‐Cys(S‐farnesylazide)‐Val‐Ile‐Ala‐OH with 2‐diphenylphosphanylbenzoic acid methyl ester then gives a stable alkoxy‐imidate linked product. This result suggests future generations whereby azide groups introduced using this enzymatic approach are functionalized using a broad range of azide‐reactive reagents. Thus, chemistry has been developed that could be used to achieve highly specific peptide and protein modification. The farnesylazide analog may be useful in certain biological studies, whereas the geranylazide group may be more useful for general protein modification and immobilization.
ISSN:1397-002X
1399-3011
DOI:10.1111/j.1399-3011.2005.00261.x