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Abstract: This paper
reports on a systemic screen for potent and selective dipeptidyl peptidase (DPP) II
inhibitors. The boronic acid derivative boroNorvaline (boroNva) was designated as the P1
position amino acid and a library of amino acids, both natural and synthetic, were
coupled with boroNva to form dipeptide inhibitors. The inhibitors were tested against
the members of the DPPIV activity ... read moreand/or structure homolog (DASH) enzymes and the 20S
proteasome. It was found that the boroNva based compounds had strong potency for DPPII,
especially Methionine (Met)-boroNva (6) and Leucine (Leu)-boroNva (10), but suffered
from poor selectivity. The selectivity for DPPII was improved when α, α
carbon di-substituted amino acids were coupled with boroNva. These small molecules can
help provide a new route for increased selectivity of boronic acid derivatives, and
ultimately facilitate our understanding of DPPII's role in biological
systems.
Thesis (M.S.)--Tufts University,
2016.
Submitted to the Dept. of Pharmacology &
Experimental Therapeutics.
Advisor: William
Bachovchin.
Committee: David
Greenblatt.
Keywords: Biochemistry, and Organic
chemistry.read less
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