albumin - publications

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A new designed modifier prolongs the action of short-lived peptides and proteins by allowing their binding to serum albumin.


Bioconjug Chem. 2012 Jul 3;


Authors: Shechter Y, Sasson K, Lev-Goldman V, Rubinraut S, Rubinstein M, Fridkin M


Abstract

We found that human serum albumin (HSA) contains a single binding domain for derivatives of long-chain fatty acid (LCFA)-like molecules in which the carboxylate is replaced by sulfonate. Accordingly, we have synthesized 16-sulfo-hexadecanoic acid-N-hydroxysuccinimide ester [HO(3)S-(CH(2))(15)-CONHS], an agent that reacts selectively with the amino side chains of peptides and proteins. A macromolecule containing a single 16-sulfo- hexadecanoate moiety associating with albumin with a Ka value of 0.83±0.08×10(6)M(-1), a sufficient affinity to extend the actions in vivo of such short-lived peptides and proteins. Subcutaneous administration of insulin-NHCO-(CH(2))(15)-SO(3)(-) into mice facilitated a glucose-lowering effect 4.3 times in duration and 6.6 times in area under the curve (AUC) as compared to in vitro equipotent amount of Zn(2+)-free insulin. Similarly, subcutaneous and intravenous administration of exendin-4-NHCO-(CH(2))(15)-SO(3)(-) to mice yielded prolonged and stable reduction in glucose level, 5-9 fold longer than that of exendin-4. Also, a single subcutaneous administration of human interferon-α2-[NH-CO-(CH(2))(15)-SO(3)(-)](3) to mice yielded circulating antiviral activity over a period of 40 hrs. In conclusion, a simple, hydrophilic reagent has been engineered, synthesized and studied. Its linkage to peptides and proteins in a mono-modified fashion, yielded hydrophilic, prolonged acting derivatives, due to their acquired ability to associate with serum albumin after administration.

PMID: 22759320 [PubMed - as supplied by publisher]