Selection of a potential diagnostic biomarker for HIV infection from a random library of non-biological synthetic peptoid oligomers.

Abstract:

:Non-biological synthetic oligomers can serve as ligands for antibodies. We hypothesized that a random combinatorial library of synthetic poly-N-substituted glycine oligomers, or peptoids, could represent a random "shape library" in antigen space, and that some of these peptoids would be recognized by the antigen-binding pocket of disease-specific antibodies. We synthesized and screened a one bead one compound combinatorial library of peptoids, in which each bead displayed an 8-mer peptoid with ten possible different amines at each position (10(8) theoretical variants). By screening one million peptoid/beads we found 112 (approximately 1 in 10,000) that preferentially bound immunoglobulins from human sera known to be positive for anti-HIV antibodies. Reactive peptoids were then re-synthesized and rigorously evaluated in plate-based ELISAs. Four peptoids showed very good, and one showed excellent, properties for establishing a sero-diagnosis of HIV. These results demonstrate the feasibility of constructing sero-diagnostic assays for infectious diseases from libraries of random molecular shapes. In this study we sought a proof-of-principle that we could identify a potential diagnostic antibody ligand biomarker for an infectious disease in a random combinatorial library of 100 million peptoids. We believe that this is the first evidence that it is possible to develop sero-diagnostic assays - for any infectious disease - based on screening random libraries of non-biological molecular shapes.

journal_name

J Immunol Methods

authors

Gearhart TL,Montelaro RC,Schurdak ME,Pilcher CD,Rinaldo CR,Kodadek T,Park Y,Islam K,Yurko R,Marques ET Jr,Burke DS

doi

10.1016/j.jim.2016.05.001

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

85-9

eissn

0022-1759

issn

1872-7905

pii

S0022-1759(16)30093-X

journal_volume

435

pub_type

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