![]() PRODUCT FOCUS: MONOCLONAL ANTIBODIES, FRAGMENTS, AND OTHER PROTEINS Since their introduction, many of those products - including Remicade, Enbrel, and other drugs - have attained blockbuster status. The first MAbs to be commercialized in the early 2000s were chimeric MAbs (genetically engineered hybrid molecules containing murine and human sequences) and “humanized” MAbs (containing 90–95% human antibody protein sequences). Keywords: Cyclotides, cyclic peptides, peptide therapeutics, drug discovery, drug design, cysteine residues, enzymatic degradation, anti-HIV, cystine-knot scaffold, neurotensin antagonism The present review reports recent findings in the biological diversity and therapeutic potential of natural and engineered cyclotides.Ĭyclotides are a unique and growing family of backbone cyclized peptides that also contain a cystine knot motif built from six conserved cysteine residues.Table 1: Commercialized monoclonal antibodies in the United States and European Union () Title: Cyclotides, a Novel Ultrastable Polypeptide Scaffold for Drug DiscoveryĪuthor(s): Andrew Gould, Yanbin Ji, Teshome L. CamareroĪbstract: Cyclotides are a unique and growing family of backbone cyclized peptides that also contain a cystine knot motif built from six conserved cysteine residues. This unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Aside from the conserved residues forming the cystine knot, cyclotides have been shown to have high variability in their sequences. Consisting of over 160 known members, cyclotides have many biological activities, ranging from anti-HIV, antimicrobial, hemolytic, and uterotonic capabilities additionally, some cyclotides have been shown to have cell penetrating properties. Originally discovered and isolated from plants, cyclotides can also be produced synthetically and recombinantly. The high sequence variability, stability, and cell penetrating properties of cyclotides make them potential scaffolds to be used to graft known active peptides or engineer peptide-based drug design. The present review reports recent findings in the biological diversity and therapeutic potential of natural and engineered cyclotides.Small near-infrared (NIR) fluorescent proteins (FPs) are much needed as protein tags for imaging applications. We developed a 17 kDa NIR FP, called miRFP670nano3, which brightly fluoresces in mammalian cells and enables deep-brain imaging. By exploring miRFP670nano3 as an internal tag, we engineered 32 kDa NIR fluorescent nanobodies, termed NIR-Fbs, whose stability and fluorescence strongly depend on the presence of specific intracellular antigens. NIR-Fbs allowed background-free visualization of endogenous proteins, detection of viral antigens, labeling of cells expressing target molecules and identification of double-positive cell populations with bispecific NIR-Fbs against two antigens. Altogether, NIR-Fbs enable the detection and manipulation of a variety of cellular processes based on the intracellular protein profile.Īpplying NIR-Fbs as destabilizing fusion partners, we developed molecular tools for directed degradation of targeted proteins, controllable protein expression and modulation of enzymatic activities. Optical imaging with near-infrared (NIR) fluorescent proteins (FPs) provides increased tissue penetration depths and a better signal‐to‐noise ratio due to reduced light-scattering, tissue absorption and autofluorescence in the NIR region (650–900 nm) 1, 2. NIR FPs allow labeling of whole organisms, specific cell populations, organelles or individual proteins, and enable spectral multiplexing with FPs, biosensors and optogenetic tools active in the visible range 1.
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