Panayotis G. Katsoyannis

Bio: Panayotis G. Katsoyannis is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Insulin & Insulin receptor. The author has an hindex of 33, co-authored 91 publications receiving 3631 citations. Previous affiliations of Panayotis G. Katsoyannis include New York University.

Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists

Abstract: The C-terminal segment of the human insulin receptor α-chain (designated αCT) is critical to insulin binding as has been previously demonstrated by alanine scanning mutagenesis and photo-cross-linking. To date no information regarding the structure of this segment within the receptor has been available. We employ here the technique of thermal-factor sharpening to enhance the interpretability of the electron-density maps associated with the earlier crystal structure of the human insulin receptor ectodomain. The αCT segment is now resolved as being engaged with the central β-sheet of the first leucine-rich repeat (L1) domain of the receptor. The segment is α-helical in conformation and extends 11 residues N-terminal of the classical αCT segment boundary originally defined by peptide mapping. This tandem structural element (αCT-L1) thus defines the intact primary insulin-binding surface of the apo-receptor. The structure, together with isothermal titration calorimetry data of mutant αCT peptides binding to an insulin minireceptor, leads to the conclusion that putative “insulin-mimetic” peptides in the literature act at least in part as mimics of the αCT segment as well as of insulin. Photo-cross-linking by novel bifunctional insulin derivatives demonstrates that the interaction of insulin with the αCT segment and the L1 domain occurs in trans, i.e., these components of the primary binding site are contributed by alternate α-chains within the insulin receptor homodimer. The tandem structural element defines a new target for the design of insulin agonists for the treatment of diabetes mellitus.

Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acids

Abstract: 9-Fluorenylmethoxycarbonyl (Fmoc) amino acids were first used for solid phase peptide synthesis a little more than a decade ago. Since that time, Fmoc solid phase peptide synthesis methodology has been greatly enhanced by the introduction of a variety of solid supports, linkages, and side chain protecting groups, as well as by increased understanding of solvation conditions. These advances have led to many impressive syntheses, such as those of biologically active and isotopically labeled peptides and small proteins. The great variety of conditions under which Fmoc solid phase peptide synthesis may be carried out represents a truly "orthogonal" scheme, and thus offers many unique opportunities for bioorganic chemistry.

Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade

Abstract: Peptides and proteins have been found to possess an inherent tendency to convert from their native functional states into intractable amyloid aggregates. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidoses. In this review, we describe this field of science with particular reference to the advances that have been made over the last decade in our understanding of its fundamental nature and consequences. We list the proteins that are known to be deposited as amyloid or other types of aggregates in human tissues and the disorders with which they are associated, as well as the proteins that exploit the amyloid motif to play specific functional roles in humans. In addition, we summarize the genetic factors that have provided insight into the mechanisms of disease onset. We describe recent advances in our knowledge of the structures of amyloid fibrils and their oligomeric precursors a...

Solid phase synthesis

Abstract: The proteins, as the Greek root of their name implies, are of first rank in living systems, and their smaller relatives, the peptides, have now also been discovered to have important roles in biology. Among their members are many of the hormones, releasing factors, growth factors, ion carriers, antibiotics, toxins, and neuropeptides. My purpose today is to describe the chemical synthesis of peptides and proteins and to discuss the use of the synthetic approach to answer various biological questions. The story begins with Emil Fischer (1) at the turn of this century when he synthesized the first peptide and coined the name. The general chemical requirements were to block the carboxyl group of one amino acid and the amino group of the second amino acid. Then, by activation of the free carboxyl group the peptide bond could be formed, and selective removal of the two protecting groups would lead to the free dipeptide. Fischer himself was never able to find a suitable reversible blocking group for the amine function, but his former student Max Bergmann, with Zervas, was successful (2). Their design of the carbobenzoxy group ushered in a new era. When I began working on the synthesis of peptides many years later this same general scheme was universally in use and was very effective, having led, for example, to the first synthesis of a peptide hormone by Du Vigneaud in 1953 (3). It soon became clear to me, however, that such syntheses were difficult and time consuming and that a new approach was needed if large numbers of peptides were required or if larger and more complex peptides were to be made.

Acog practice bulletin

Abstract: Critical care in pregnancy is a field that remains unevenly researched. Although there is a body of evidence to guide many recommendations in critical care, limited research specifically addresses obstetric critical care. The purpose of this document is to review the available evidence, propose strategies for care, and highlight the need for additional research. Much of the review will, of necessity, focus on general principles of critical care, extrapolating where possible to obstetric critical care.