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The reaction of protein amino groups with methyl 5-iodopyridine-2-carboximidate. A possible general method of preparing isomorphous heavy-atom derivatives of proteins.

ABSTRACT: 1. The synthesis of methyl 5-iodopyridine-2-carboximidate and its reaction with amino groups of model compounds and performic acid-oxidized insulin are described. The reagent was designed to introduce heavy atoms into specific sites in proteins. 2. Specific reaction with the amino groups of oxidized insulin can be achieved under reasonably mild conditions giving rise to the corresponding N-monosubstituted amidines. 3. The extent of reaction of this reagent with protein amino groups can be readily determined by difference spectroscopy. Modification of lysine residues inhibits tryptic cleavage at such residues, and this can be of assistance in establishing the site of modification in the primary structure. 4. Evidence is presented to show that methyl 5-iodopyridine-2-carboximidate can react specifically, at pH5.0, with the aromatic amino group of 3-amino-l-tyrosine; the final product of this reaction is a 2-arylbenzoxazole. 5. The use of this reagent as a general method for preparing heavy-atom isomorphous derivatives of proteins is discussed.

SUBMITTER: Riley M

PROVIDER: S-EPMC1177523 | biostudies-other | 1973 Apr

REPOSITORIES: biostudies-other

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A general method for phasing novel complex RNA crystal structures without heavy-atom derivatives.

Project description:The crystallographic phase problem [Muirhead & Perutz (1963), Nature (London), 199, 633-638] remains the single major impediment to obtaining a three-dimensional structure of a macromolecule once suitable crystals have been obtained. Recently, it was found that it was possible to solve the structure of a 142-nucleotide L1 ligase ribozyme heterodimer that possesses no noncrystallographic symmetry without heavy-atom derivatives, anomalous scattering atoms or other modifications and without a model of the tertiary structure of the ribozyme [Robertson & Scott (2007), Science, 315, 1549-1553]. Using idealized known RNA secondary-structural fragments such as A-form helices and GNRA tetraloops in an iterative molecular-replacement procedure, it was possible to obtain an estimated phase set that, when subjected to solvent flattening, yielded an interpretable electron-density map with minimized model bias, allowing the tertiary structure of the ribozyme to be solved. This approach has also proven successful with other ribozymes, structured RNAs and RNA-protein complexes.

| S-EPMC2507861 | biostudies-literature

Exploiting subtle structural differences in heavy-atom derivatives for experimental phasing.

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General and Direct Method for Preparing Oligonucleotide-Functionalized Metal-Organic Framework Nanoparticles.

Project description:Metal-organic frameworks (MOFs) are a class of modular, crystalline, and porous materials that hold promise for storage and transport of chemical cargoes. Though MOFs have been studied in bulk forms, ways of deliberately manipulating the external surface functionality of MOF nanoparticles are less developed. A generalizable approach to modify their surfaces would allow one to impart chemical functionality onto the particle surface that is independent of the bulk MOF structure. Moreover, the use of a chemically programmable ligand, such as DNA, would allow for the manipulation of interparticle interactions. Herein, we report a coordination chemistry-based strategy for the surface functionalization of the external metal nodes of MOF nanoparticles with terminal phosphate-modified oligonucleotides. The external surfaces of nine distinct archetypical MOF particles containing four different metal species (Zr, Cr, Fe, and Al) were successfully functionalized with oligonucleotides, illustrating the generality of this strategy. By taking advantage of the programmable and specific interactions of DNA, 11 distinct MOF particle-inorganic particle core-satellite clusters were synthesized. In these hybrid nanoclusters, the relative stoichiometry, size, shape, and composition of the building blocks can all be independently controlled. This work provides access to a new set of nucleic acid-nanoparticle conjugates, which may be useful as programmable material building blocks and as probes for measuring and manipulating intracellular processes.

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A general strategy for preparing pyrrolic-N<sub>4</sub> type single-atom catalysts via pre-located isolated atoms.

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| S-EPMC8611002 | biostudies-literature

Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect.

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| S-EPMC8467094 | biostudies-literature

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ANODE: anomalous and heavy-atom density calculation.

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