发信人: Marble (小石头哥哥), 信区: Biology
标 题: Re: De NOVO drug (peptide) design
发信站: The unknown SPACE (Sat Apr 13 15:13:44 2002), 站内信件

talking about de novo peptide-derived drug design, i have an
idea using biosensor for such investigation. basically, i
would like to assess and evaluate the binding affinity of the
peptide to the known receptor as well as its downstream signaling
transductivity. so i may design two chips (biomembrane-based),
both approapriately covered by the receptors, with one linking
to some biosensor that basically detect the affinity, while the
other coupled to the primary downstream signal transducer while
the signal could be recorded. the idea of designing homologs
for the hormone might not be necessary, given the fact once the
critical binding sites have been determined, and components of
all the other amino acid residues can alter the affinity as well
as downstream effect. so randomly designed and synthesized
peptides might be helpful. and i would run the assay on some
96-well like biochip, given the threshold for evaluation and
find the best one(s) that have both enough affinity and proper
biological activity for further cell culture/animal model experiment.

【 在 leohawk (leohawk) 的大作中提到: 】
: No reference that I know about, the technique is not hard, just require
: large work flow and luck.
: The peptide(s) that show biological activity are totally novel... no homolog
: at all, and this makes me question the design of partner based on
: homology.
: Cell surface receptor and ligand interaction is complicated, sometimes,
: high affinity doesn't guarantee good activity as after binding, the complex
: should be internalized such that terminate the cascade of secondary
: signal transduction... otherwise, it may lead to disaster. So, to be a good
: ligand, high affinity is absolutely not enough.
: I looked at blaudonau's suggestion, but I am not sure it is the same
: as I said.
: 【 在 iblicf (空中大灌篮) 的大作中提到: 】
: : What I'm concerning about is whether this work (idea) has market potential or
: : not. Or, if it's applicable or can raise investor's interest or not. leohawk's
: : talk confuse me a little, can you guys give out some referrence about this
: : idea? That'll be helpful.
: : BTW, I'm dealing with peptide and cell surface binding as well. And recently
: : our group seems to be stuck on sth.
: : don't
: : we
: : not


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