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Hi there -
I would tend to agree with George that, a peptide that mimics the
short helix is by far the easiest to try.
getting a small molecule to do so is a few years work anyway ;-)
The main source of trouble with the peptide might only be if its too
hydrophobic to dissolve;
helices usually are not, but helices that like other proteins can be.
I do have my doubts however if this will work - although its try-
worthy - and in what context.
for example, Its also as Artem points out a kon/koff issue.
Don't forget that, for example, kon is concentration dependent,
while koff is not. So, it would be worth doing (or digging the
literature for)
a thermodynamic characterization (ITC) and/or binding properties (SPR)
of the complex before embarking to the adventure of disrupting it.
having said these, order the peptide before going to the library
though ;-)
A.
On May 2, 2006, at 9:36, George Kontopidis wrote:
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I will recommend you to go ahead and try a peptide that mimic the
sort helix of one of the partners.
It is unlikely to discover in a sort time a small molecule, which
can do the same thing.
Best wishes
George
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] Behalf Of
[EMAIL PROTECTED]
Sent: 01 May 2006 17:40
To: [email protected]
Subject: [ccp4bb]: Disrupting a protein complex with a peptide
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Dear All :
Sorry for this non-CCP4 question.
I am dealing with a protein binary complex, with known structure.
We know
that the interaction between both partners is processed via a short
helix.
OK, let's imagine that we would like to disrupt this interaction in
vitro.
I was thinking in using a peptide that will mimic the short helix
of one
of the partners to block the other one.
Is it a crazy idea ?. Anyone has dealed with something like that
with the
same approach ?. Is it better to use peptides to disrupt protein
complexes, or we could use small molecules as well ?. Any rational
(but
easy, for dummies level) approach to design the peptide that blocks
the
complex formation ?.
I would appreciate some help and comments about that.
Many, many thanks
Cheers
Francisco
-----------------------------------------
Francisco J. Enguita, Ph.D.
Host-pathogen Interactions Group
Macromolecular Crystallography Laboratory
ITQB
EAN, Av. da República
2781-901 Oeiras
Portugal
Phone : +351-21-4469663
Fax : +351-21-4433644
E-mail : [EMAIL PROTECTED]
-----------------------------------------
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