Mathai Mammen

Bio: Mathai Mammen is an academic researcher from Harvard University. The author has contributed to research in topics: Agonist & Muscarinic acetylcholine receptor. The author has an hindex of 28, co-authored 86 publications receiving 7834 citations.

Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors.

Abstract: Found throughout biology, polyvalent interactions are characterized by the simultaneous binding of multiple ligands on one biological entity to multiple receptors on another (top part of the illustration) and have a number of characteristics that monovalent interactions do not (bottom). In particular, polyvalent interactions can be collectively much stronger than corresponding monovalent interactions, and they can provide the basis for mechanisms of both agonizing and antagonizing biological interactions that are fundamentally different from those available in monovalent systems.

Noncovalent Synthesis: Using Physical-Organic Chemistry To Make Aggregates

Abstract: A molecule is usually understood to be a stable collection of atoms connected bv a continuous network of covalent bonds. The develipment of methods for constructing these networks has been a central occupation of organic chemistry, and the success of these methods has made possible the power, elegance, and utility of modern organic synthesis. The preparations of vitamin B12,l palytoxin,2 calicheamicin,3 and other complex secondary metabolites illustrate the extraordinary sophistication of this field. This type of synthesis-which we refer to as covalent synthesis, in the absence of a better termcontinues to expand its capabilities, but it may be understandably difficult to provide very large and structurally complex molecules quickly and economically by using it.4 Organic chemistry has always taken much of its inspiration and motivation from Nature. As biological molecules-especially large molecules having complex tertiary structures such as proteins, DNA, and RNA-have become central concerns of organic chemistry, noncovalent interactions have moved toward the center of attention. Although biological macromolecules are largely composed of Covalent bonds, the networks of these bonds are not always continuous, and many important structures-including multimeric proteins and DNA itself-are "aggregates" and not simply "molecules". Many biological molecules and aggregates derive much of their unique structure and function from noncovalent interactions: that is, from

Polyvalente Wechselwirkungen in biologischen Systemen: Auswirkungen auf das Design und die Verwendung multivalenter Liganden und Inhibitoren

Abstract: Uberall in der Biologie kommen polyvalente Wechselwirkungen vor. Sie zeichnen sich durch die gleichzeitige Bindung mehrerer Liganden einer biologischen Einheit an mehrere Rezeptoren einer anderen biologischen Einheit aus (oberer Teil der Graphik) und haben eine Reihe von Charakteristika, die monovalenten Wechselwirkungen fehlen (unten). Besonders im Verbund konnen polyvalente Wechselwirkungen viel starker sein als entsprechende monovalente Wechselwirkungen, und sie konnen die Basis fur das Verstandnis fordernder und hemmender biologischer Wechselwirkungen liefern, die sich grundsatzlich von denen in monovalenten Systemen unterscheiden.

Effective Inhibitors of Hemagglutination by Influenza Virus Synthesized from Polymers Having Active Ester Groups. Insight into Mechanism of Inhibition

Abstract: Highly effective sialic acid-containing inhibitors of influenza virus X-31 were synthesized using poly[N-(acryoyloxy)succinimide] (pNAS), a polymer preactivated by incorporation of active ester groups. Polymers containing two and three different components were prepared by sequential reaction of pNAS with two and three amines, respectively. This preparation of co- and terpolymers was synthetically more efficient than methods involving copolymerization of different monomers and gave polymers that were more easily compared than those generated by copolymerization. Polymers in this study (prepared from a single batch of pNAS) had a constant degree of polymerization (DP approximately 2000) and probably had a distribution of components that was more random than analogous polymers prepared by copolymerization. Use of C-glycosides of sialic acid made it possible to investigate inhibition by different polymers at temperatures ranging from 4 to 36 degrees C without artifacts due to the hydrolytic action of neuraminidase. The inhibitors were, in general, more effective at 36 degrees C than at 4 degrees C. The hemagglutination (HAI) assay was used to measure the value of the inhibition constant KHAIi each polymer. The value of KHAIi for the two-component polymer containing 20% sialic acid on a polyacrylamide backbone at 4 degrees C was 4 nM (in terms of the sialic acid moieties present in solution) and was approximately 50-fold more effective than the best inhibitors previously described and 25-fold more effective than the best naturally occurring inhibitor. The most effective inhibitor synthesized in this work contained 10% benzyl amine and 20% sialic acid on a polyacrylamide backbone, and its value of KHAIi was 600 pM at 36 degrees C. Approximately 100 polymers that differed in one or two components were assayed to distinguish between two limiting mechanisms for inhibition of the interaction between the surfaces of virus and erythrocytes: high-affinity binding through polyvalency, and steric stabilization. The results suggest that both mechanisms play an important role. The system comprising polyvalent inhibitors of agglutination of erythrocytes by influenza provides a system that may be useful as a model for inhibitors of other pathogen-host interactions, a large number of which are themselves polyvalent.

Estimating the Entropic Cost of Self-Assembly of Multiparticle Hydrogen-Bonded Aggregates Based on the Cyanuric Acid·Melamine Lattice

Abstract: The entropic component of the free energy of assembly for multiparticle hydrogen-bonded aggregates is analyzed using a model based on balls connected by rigid rods or flexible strings. The entropy of assembly, ΔS, is partitioned into translational, rotational, vibrational, and conformational components. While previously reported theoretical treatments of rotational and vibrational entropies for assembly are adequate, treatments of translational entropy in solution and of conformational entropyoften the two largest components of ΔSare not. This paper provides improved estimates and illustrates the methods used to obtain them. First, a model is described for translational entropy of molecules in solution (ΔStrans(sol)); this model provides physically intuitive corrections for values of ΔStrans(sol) that are based on the Sackur−Tetrode equation. This model is combined with one for rotational entropy to estimate the difference in entropy of assembly between a 4-particle aggregate and a 6-particle one. Second,...

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

Abstract: This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...

Shape‐Controlled Synthesis of Metal Nanocrystals: Simple Chemistry Meets Complex Physics?

Abstract: Nanocrystals are fundamental to modern science and technology. Mastery over the shape of a nanocrystal enables control of its properties and enhancement of its usefulness for a given application. Our aim is to present a comprehensive review of current research activities that center on the shape-controlled synthesis of metal nanocrystals. We begin with a brief introduction to nucleation and growth within the context of metal nanocrystal synthesis, followed by a discussion of the possible shapes that a metal nanocrystal might take under different conditions. We then focus on a variety of experimental parameters that have been explored to manipulate the nucleation and growth of metal nanocrystals in solution-phase syntheses in an effort to generate specific shapes. We then elaborate on these approaches by selecting examples in which there is already reasonable understanding for the observed shape control or at least the protocols have proven to be reproducible and controllable. Finally, we highlight a number of applications that have been enabled and/or enhanced by the shape-controlled synthesis of metal nanocrystals. We conclude this article with personal perspectives on the directions toward which future research in this field might take.