Subject: CCL: scoring for "peptide-likeness"

From: [email-masked] (Robert Bywater)
Date: Wed, 28 Jul 1999 07:27:39 +0200 (MEST)

Hello CCLers, especially those interested in peptide mimics/analogs.

We read and hear a lot about 'non-petide' or 'peptide-like' drugs or
peptide mimics/analogs.

But what exactly are these animals ? Who has defined what is peptide-like
and not-peptide-like ? What were these definitions ? What scoring function
is used by people out there to say how like or unlike a peptide your drug
is ?

I have seen examples of dozens of ligands that bind e.g. to proteases
that are not (apparently) peptides. For example, oligosaccharides will
bind very nicely to trypsin in the binding groove for the normal
oligopeptide substrate. A close homolog of elastase, called heparin-binding
protein (lacks the catalytic serine residue, but otherwise folds like
elastase) does just that: it binds heparin, in much the same way as
elastase binds its oligopeptide substrate. Doesn't that make heparin (and
the other oligosaccharides mentioned above) peptide-like ? But how
much like a peptide is it, quantitatively ?

Of course, anthing lacking at least one peptide bond and having no natural
amino acid residue-type sidechain would be classified as a "non-peptide"
but it may be "peptide-like" in its behaviour. If anyone out there has any
ideas on this, a scoring function maybe or even a definition of "peptide-
likeness", could they share that with us ? I will summarise the replies I
get and post these.

Best regards

Robert Bywater

-- 

############################################################################
from:  Robert Bywater PhD  
       Biostructure Department 
       Novo Nordisk A/S

email: [email-masked]

tel  : +45 4443 4530                          fax  : +45 4443 4547

GPS coordinates: N 55 deg 45.312' E 12 deg 15.021' altitude  155 ft asl 

snailmail: 
           Novo Nordisk A/S
           Novo Nordisk Park  (G8.2.76)
           DK-2760 MAALOEV Denmark 
############################################################################