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Dive into the research topics where Anna-Maria A. Hays Putnam is active.

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Featured researches published by Anna-Maria A. Hays Putnam.


Proceedings of the National Academy of Sciences of the United States of America | 2011

Optimized clinical performance of growth hormone with an expanded genetic code

Ho Cho; Tom Daniel; Ying Buechler; David C. Litzinger; Zhenwei Maio; Anna-Maria A. Hays Putnam; Bee-Cheng Sim; Stuart Bussell; Tsotne Javahishvili; Sami Kaphle; Guillermo Viramontes; Mike Ong; Stephanie Chu; Becky Gc; Ricky Lieu; Nick Knudsen; Paola Castiglioni; Thea Norman; Douglas W. Axelrod; Andrew R. Hoffman; Peter G. Schultz; Richard D. DiMarchi; Bruce E. Kimmel

The ribosomal incorporation of nonnative amino acids into polypeptides in living cells provides the opportunity to endow therapeutic proteins with unique pharmacological properties. We report here the first clinical study of a biosynthetic protein produced using an expanded genetic code. Incorporation of p-acetylphenylalanine (pAcF) at distinct locations in human growth hormone (hGH) allowed site-specific conjugation with polyethylene glycol (PEG) to produce homogeneous hGH variants. A mono-PEGylated mutant hGH modified at residue 35 demonstrated favorable pharmacodynamic properties in GH-deficient rats. Clinical studies in GH-deficient adults demonstrated efficacy and safety comparable to native human growth hormone therapy but with increased potency and reduced injection frequency. This example illustrates the utility of nonnative amino acids to optimize protein therapeutics in an analogous fashion to the use of medicinal chemistry to optimize conventional natural products, low molecular weight drugs, and peptides.


Diabetes | 2012

FGF21 Analogs of Sustained Action Enabled by Orthogonal Biosynthesis Demonstrate Enhanced Antidiabetic Pharmacology in Rodents

James Mu; Jason Pinkstaff; Zhihua Li; Lillian Skidmore; Nina Li; Heather Myler; Qing Dallas-Yang; Anna-Maria A. Hays Putnam; Jun Yao; Stuart Bussell; Margaret Wu; Thea Norman; Carlos G. Rodriguez; Bruce E. Kimmel; Joseph M. Metzger; Anthony Manibusan; Darin Lee; Dennis M. Zaller; Bei B. Zhang; Richard D. DiMarchi; Joel P. Berger; Douglas W. Axelrod

Fibroblast growth factor 21 (FGF21) mitigates many of the pathogenic features of type 2 diabetes, despite a short circulating half-life. PEGylation is a proven approach to prolonging the duration of action while enhancing biophysical solubility and stability. However, in the absence of a specific protein PEGylation site, chemical conjugation is inherently heterogeneous and commonly leads to dramatic loss in bioactivity. This work illustrates a novel means of specific PEGylation, producing FGF21 analogs with high specific activity and salutary biological activities. Using homology modeling and structure-based design, specific sites were chosen in human FGF21 for site-specific PEGylation to ensure that receptor binding regions were preserved. The in vitro activity of the PEGylated FGF21 ana-logs corresponded with the site of PEG placement within the binding model. Site-specific PEGylated analogs demonstrated dramatically increased circulating half-life and enhanced efficacy in db/db mice. Twice-weekly dosing of an optimal FGF21 analog reduced blood glucose, plasma lipids, liver triglycerides, and plasma glucagon and enhanced pancreatic insulin content, islet number, and glucose-dependent insulin secretion. Restoration of insulin sensitivity was demonstrated by the enhanced ability of insulin to induce Akt/protein kinase B phosphorylation in liver, muscle, and adipose tissues. PEGylation of human FGF21 at a specific and preferred site confers superior metabolic pharmacology.


Archive | 2008

Modified fgf-21 polypeptides and their uses

Thomas P. Cujec; Roberto Mariani; Anna-Maria A. Hays Putnam; William M. Keefe; Nick Knudsen; Lillian Ho; Jason Pinkstaff


Archive | 2007

Modified human plasma polypeptide or fc scaffolds and their uses

Joseph Sheffer; Thea Norman; Richard D. DiMarchi; Anna-Maria A. Hays Putnam; Feng Tian; Stephanie Chu; Denise Krawitz; Ho Sung Cho


Archive | 2009

Modified FGF-23 Polypeptides and Their Uses

Jason Pinkstaff; Anna-Maria A. Hays Putnam; Kristin S Eaton


Archive | 2008

Modified insulin polypeptides and their uses

Zhenwei Miao; Denise Krawitz; Feng Tian; Bee-Cheng Sim; Lillian Skidmore; Anna-Maria A. Hays Putnam; Nick Knudsen; Michael Deguzman


Archive | 2006

Methods and compositions comprising non-natural amino acids

Zhenwei Miao; Feng Tian; Anna-Maria A. Hays Putnam; Ying Buechler


Archive | 2009

Modified leptin polypeptides and their uses

Anna-Maria A. Hays Putnam; Nick Knudsen; Jason Pinkstaff; Heather Myler; Lorraine Sullivan


Archive | 2009

Modified bovine g-csf polypeptides and their uses

Anna-Maria A. Hays Putnam; Nick Knudsen; Thea Norman; Alan Koder; Lillian Ho; Peter C. Canning


Archive | 2008

Modified interferon beta polypeptides and their uses

Nick Knudsen; Anna-Maria A. Hays Putnam; Denise Krawitz; Jason Pinkstaff; Heather Myler

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Jason Pinkstaff

Scripps Research Institute

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Feng Tian

Scripps Research Institute

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Thea Norman

University of California

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Richard D. DiMarchi

Indiana University Bloomington

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Stephanie Chu

Scripps Research Institute

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