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  4. Systematic Modulation of Michael-Type Reactivity of Thiols through the Use of Charged Amino Acids
 
research article

Systematic Modulation of Michael-Type Reactivity of Thiols through the Use of Charged Amino Acids

Lutolf, M. P.  
•
Tirelli, N.
•
Cerritelli, S.
Show more
2001
Bioconjugate Chemistry

A quant. structure-reactivity relationship for the Michael-type addn. of thiols onto acrylates was detd. Several thiol-contg. peptides were investigated by examg. the correlation between the second-order rate const. of their addn. onto PEG-diacrylate and the pKa of the thiols within a peptide. By introducing charged amino acids in close proximity to a cysteine, the pKa of the thiol was systematically modulated by electrostatic interactions. Pos. charges from the amino acid arginine decreased the pKa of the thiol and accelerated the reaction with acrylates while neg. charges from aspartic acids showed the opposite effect. A linear correlation between thiolate concns. and kinetic consts. was found, confirming the role of thiolates as the reactive species in this Michael-type reaction. The relevant factors influencing the reactivity were the sign and the no. of the neighboring charges, while the position of these charges had little effect on reactivity. These results provide a basis for the rational design of peptides, where the kinetics, and thus, selectivity of protein/peptide conjugation with polymeric structures via Michael-type addn. reactions can be controlled. [on SciFinder (R)]

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Type
research article
DOI
10.1021/bc015519e
Author(s)
Lutolf, M. P.  
Tirelli, N.
Cerritelli, S.
Colussi, L.
Hubbell, J. A.  
Date Issued

2001

Published in
Bioconjugate Chemistry
Volume

12

Issue

6

Start page

1051

End page

1056

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LMRP  
UPLUT  
Available on Infoscience
February 27, 2006
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/226567
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