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Colleague of mine have had a positive experience with cyclic peptides
that remained helical upon slight extension for cyclization purposes.
It could be worth trying. Savvas N. Savvides wrote: *** For details on how to be removed from this list visit the *** *** CCP4 home page http://www.ccp4.ac.uk ***Dear Francisco, I think the native peptide approach can be as adventurous and perilous as the 'small molecule' idea because it would be based on the assumption that the peptide will spontaneously fold into a short helix. I do not think that you can assume that in the absence of the rest of the protein and, for that matter, the binding partner! It is not uncommon for short helices at a complex interface to adopt their helical structure only upon complex formation! What usually facilitates the loop-->helix transition in those cases is the presence of a complete protein landscape on both sides of the ball! I recently came across the following paper which, in addition to some spectacular results, highlights the challenges of trying to agonize or antagonize an interaction that is otherwise routine for mother nature. Walensky LD, et al. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science. 2004, 305(5689):1466-70. Best wishes Savvas -----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]] On Behalf Of Anastassis Perrakis Sent: dinsdag 2 mei 2006 10:46 To: George Kontopidis Cc: [EMAIL PROTECTED]; [email protected] Subject: Re: [ccp4bb]: Disrupting a protein complex with a peptide *** For details on how to be removed from this list visit the *** *** CCP4 home page http://www.ccp4.ac.uk *** 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:*** For details on how to be removed from this list visit the *** *** CCP4 home page http://www.ccp4.ac.uk *** 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]]On Behalf Of[EMAIL PROTECTED] Sent: 01 May 2006 17:40 To: [email protected] Subject: [ccp4bb]: Disrupting a protein complex with a peptide *** For details on how to be removed from this list visit the *** *** CCP4 home page http://www.ccp4.ac.uk *** 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] ----------------------------------------- _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ DISCLAIMER: This e-mail contains proprietary information some or all of which may be legally privileged. It is for the intended recipient only. If an addressing or transmission error has misdirected this e-mail, please notify the author by replying to this e-mail. If you are not the intended recipient you must not use, disclose, distribute, copy, print, or rely on this e-mail. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ |
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