Insulin-like Growth Factor 2 (IGF2)-Fused Lysosomal Targeting Chimeras for Degradation of Extracellular and Membrane Proteins.

Targeted degradation of the cell-surface and extracellular proteins via the endogenous lysosomal degradation pathways, such as lysosome-targeting chimeras (LYTACs), has recently emerged as an attractive tool to expand the scope of extracellular chemical biology. Herein, we report a series of recombinant proteins genetically fused to insulin-like growth factor 2 (IGF2), which we termed iLYTACs, that can be conveniently obtained in high yield by standard cloning and bacterial expression in a matter of days. We showed that both type-I iLYTACs, in which IGF2 was fused to a suitable affibody or nanobody capable of binding to a specific protein target, and type-II iLYTAC (or IGF2-Z), in which IGF2 was fused to the IgG-binding Z domain that served as a universal antibody-binding adaptor, could be used for effective lysosomal targeting and degradation of various extracellular and membrane-bound proteins-of-interest.

Purification of Intramineral Peptides from Cuttlebones and In Vitro Activity in CaCO Biomineralization.

Living organisms develop functional hard structures such as teeth, bones, and shells from calcium salts through mineralization for managing vital functions to sustain life. However, the exact mechanism or role of biomolecules such as proteins and peptides in the biomineralization process to form defect-free hierarchical structures in nature is poorly understood. In this study, we have extracted, purified, and characterized five major peptides (CBP1-CBP5) from the soluble organic materials (SOMs) of cuttlefish bone (CB) and used for the in vitro mineralization of calcium carbonate crystals.

Stimulus-responsive self-assembled prodrugs in cancer therapy.

Small-molecule prodrugs have become the main toolbox to improve the unfavorable physicochemical properties of potential therapeutic compounds in contemporary anti-cancer drug development. Many approved small-molecule prodrugs, however, still face key challenges in their pharmacokinetic (PK) and pharmacodynamic (PD) properties, thus severely restricting their further clinical applications. Self-assembled prodrugs thus emerged as they could take advantage of key benefits in both prodrug design and nanomedicine, so as to maximize drug loading, reduce premature leakage, and improve PK/PD parameters and targeting ability.

Omics Technologies for Profiling Toxin Diversity and Evolution in Snake Venom: Impacts on the Discovery of Therapeutic and Diagnostic Agents.

Snake venoms are primarily composed of proteins and peptides, and these toxins have developed high selectivity to their biological targets. This makes venoms interesting for exploration into protein evolution and structure-function relationships. A single venom protein superfamily can exhibit a variety of pharmacological effects; these variations in activity originate from differences in functional sites, domains, posttranslational modifications, and the formations of toxin complexes.

A review of the relationships of Xenochrophis cerasogaster Cantor, 1839 (Serpentes: Colubridae) to its congeners.

We sampled snakes of the genus Xenochrophis from across Northeast India. The snakes were evaluated for both morphological and molecular parameters. Phylogenetic relationship was reconstructed using mitochondrial genes (Cytb, 12s rRNA, ND4).

Expression and characterization of haemathrins, madanin-like thrombin inhibitors, isolated from the salivary gland of tick Haemaphysalis bispinosa (Acari: Ixodidae).

Saliva of hematophagous animals, such as ticks, is an excellent source of anticoagulant proteins and polypeptides. Here we describe the identification and characterization of two thrombin inhibitors named as haemathrin 1 and 2 from the salivary gland of tick Haemaphysalis bispinosa using genomic approach. Haemathrins are cysteine-less peptide anticoagulants, which share about 65-70% identity with madanins, and belong to inhibitor I53 superfamily of inhibitors of the MEROPS database.

Venom gland transcriptomics for identifying, cataloging, and characterizing venom proteins in snakes.

Snake venoms are cocktails of protein toxins that play important roles in capture and digestion of prey. Significant qualitative and quantitative variation in snake venom composition has been observed among and within species. Understanding these variations in protein components is instrumental in interpreting clinical symptoms during human envenomation and in searching for novel venom proteins with potential therapeutic applications.

Identification and characterization of Rhipicephalus (Boophilus) microplus and Haemaphysalis bispinosa ticks (Acari: Ixodidae) of northeast India by ITS2 and 16S rDNA sequences and morphological analysis.

To investigate and identify the ticks prevalent in the North East part of India, scanning electron microscope (SEM) and DNA sequence of nuclear second internal transcribed spacer (ITS2) and mitochondrial 16S ribosomal DNA (rDNA) were used. Based on the morphological and molecular analysis, the ticks infesting cattle of North East India were found to be Rhipicephalus (Boophilus) microplus and Haemaphysalis bispinosa. ITS2 and 16S rDNA sequence from R.