Targeting the Integrin Ligand Binding Site.

2015-01-13

azim58 - Targeting the Integrin Ligand Binding Site.

location
/home/kurt/kurt/storage/laptop_L_DR/2012/11-4-12/High-affinity
self-reactive human antibodies by design and selection c Targeting the
integrin ligand binding site.pdf

Barbas, C.F., Languino, L.R., Smith, J.W., 1993. High-Affinity
Self-Reacting Human Antibodies by Design and Selection: Targeting the
Integrin Ligand Binding Site. Proceedings of the National Academy of
Sciences USA 90, 10003-10007.

High-affinity self-reactive human antibodies by design and selection:
Targeting the integrin ligand binding site
notes
11-4-12

generating antibodies to self antigens
targeted integrins

quote
We have
demonstrated that antibodies can be selected to bind small
haptens (4, 7), metal ions (6), and metal oxides by introducing
a random sequence into one or two CDRs of an antibody.

quote
The Arg-Gly-Asp (RGD) sequence is an integrin recognition
motif found in many adhesive proteins (8-11).

wow the RGD motif is found in snake venom and some viruses

? what is echistatin and tenascin?

quote
The RGD sequence was placed at Kabat positions 100 a-c
ensuring its location near the apex of the turn.

quote
four rounds of panning against immobilized receptor.

SPR was used to determine affinity

IC50 is inhibition constant

vitronectin is natural ligand of integrin

q
Fab-9 is specific to 83 integrins.

I don't fully understand why they wanted their binding between antibody
and integrin to be divalent-cation-dependent

I was surprised that RGD and RGE peptides behaved so differently in this
assay

q
This methodology is not necessarily limited to integrins, as
naturally occurring antibodies have been described that
mimic many ligands (42).

q
CDR loop can be viewed as a conformationally
constrained peptide

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