Alpha-Melanocyte Stimulating Hormone: An Emerging Anti-Inflammatory Antimicrobial Peptide

Singh, Madhuri; Mukhopadhyay, Kasturi

doi:10.1155/2014/874610

Cited by 56 publications

(40 citation statements)

References 72 publications

(164 reference statements)

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“…8, A , Targeting melanocortin receptors to control peripheral inflammation has frequently been used. Accordingly, the administration of -MSH to mice or rats with psoriasis, colitis, rheumatoid arthritis, or infections resulted in a marked amelioration of disease mediated by the suppression of pathogenic effector cells, the down-regulation of pro-inflammatory and the induction of antiinflammatory cytokines (14,(39)(40)(41). Since some immunomodulatory properties of the melanocortin system, including the induction of functional Treg (14), might be relevant to CNS inflammation as well, we assessed the therapeutic potential of NDP-MSH, a melanocortin peptide recently approved for the treatment of certain skin diseases, during established inflammatory and degenerative CNS disorders.…”

Section: Discussionmentioning

confidence: 99%

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease

et al. 2016

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“…α-MSHs are linear tridecapeptides, mainly responsible for skin pigmentation regulation [63]. α-MSHs and their analogs exhibit impressive binding affinities to melanocortin-1 receptors (MC-1r) which are expressed in over 80% of human melanoma metastases, and thus, are widely used as vehicles for melanoma-targeted imaging and radiotherapy.…”

Section: Peptides Targeting Receptors Overexpressed In Specific Camentioning

confidence: 99%

Peptide-based imaging agents for cancer detection

Sun

Liu

et al. 2017

Advanced Drug Delivery Reviews

191

151

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Selective receptor-targeting peptide based agents have attracted considerable attention in molecular imaging of tumor cells that overexpress corresponding peptide receptors due to their unique properties such as rapid clearance from circulation as well as high affinities and specificities for their targets. The rapid growth of chemistry modification techniques has enabled the design and development of various peptide-based imaging agents with enhanced metabolic stability, favorable pharmacokinetics, improved binding affinity and selectivity, better imaging ability as well as biosafety. Among them, many radiolabeled peptides have already been translated into the clinic with impressive diagnostic accuracy and sensitivity. This review summarizes the current status in the development of peptide-based imaging agents with an emphasis on the consideration of probe design including the identification of suitable peptides, the chemical modification of probes and the criteria for clinical translation. Specific examples in clinical trials have been provided as well with respect to their diagnostic capability compared with other FDA approved imaging agents.

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“…This observation reinforces a previously known structural tendency of AMPs, because several of them are known to have endocrine and homeostatic functions. For example, hepcidin permeates membranes but is also involved in regulation of iron (51), whereas ⍺-melanocyte stimulating hormone has antimicrobial and antiinflammatory effects in addition to its signaling properties (52). Calcitonin is a peptide hormone involved in calcium homeostasis, but is also a known amyloid that deposits in medullary thyroid carcinoma.…”

Section: Directed Search Of the Sequence Space Of Physicochemically Rmentioning

confidence: 99%

Mapping membrane activity in undiscovered peptide sequence space using machine learning

Lee

Fulan

Wong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

154

194

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There are some ∼1,100 known antimicrobial peptides (AMPs), which permeabilize microbial membranes but have diverse sequences. Here, we develop a support vector machine (SVM)-based classifier to investigate ⍺-helical AMPs and the interrelated nature of their functional commonality and sequence homology. SVM is used to search the undiscovered peptide sequence space and identify Pareto-optimal candidates that simultaneously maximize the distance σ from the SVM hyperplane (thus maximize its "antimicrobialness") and its ⍺-helicity, but minimize mutational distance to known AMPs. By calibrating SVM machine learning results with killing assays and small-angle X-ray scattering (SAXS), we find that the SVM metric σ correlates not with a peptide's minimum inhibitory concentration (MIC), but rather its ability to generate negative Gaussian membrane curvature. This surprising result provides a topological basis for membrane activity common to AMPs. Moreover, we highlight an important distinction between the maximal recognizability of a sequence to a trained AMP classifier (its ability to generate membrane curvature) and its maximal antimicrobial efficacy. As mutational distances are increased from known AMPs, we find AMP-like sequences that are increasingly difficult for nature to discover via simple mutation. Using the sequence map as a discovery tool, we find a unexpectedly diverse taxonomy of sequences that are just as membrane-active as known AMPs, but with a broad range of primary functions distinct from AMP functions, including endogenous neuropeptides, viral fusion proteins, topogenic peptides, and amyloids. The SVM classifier is useful as a general detector of membrane activity in peptide sequences.machine learning | membrane curvature | membrane permeation | antimicrobial peptides | cell-penetrating peptides T he ∼1,100 known antimicrobial peptides (AMPs) (1-6) are known collectively to have broad spectrum antimicrobial activity (1, 3, 5) via nonspecific interactions to target generic features in the many pathogen membranes (1, 7). Machine learning can in principle be used to help discover the "blueprint" for natural AMP sequences; however, such an enterprise presents significant structural difficulties. AMPs do not share a common core structure, but tend to be short (<50 amino acids), cationic (+2 to +9), and amphiphilic (1-6). One of the principal components of AMP activity involves the selective permeabilization of microbial membranes (1-3, 5, 8-11). However, there is increasing evidence that membrane activity is but one of several modes of antimicrobial activity: Translocated AMPs can interact with intracellular targets to inhibit cell wall synthesis, nucleic acid synthesis, protein synthesis, and enzymatic activity (12-16). Recent studies have shown that AMPs can be immunomodulatory (17, 18): In fact, LL-37 plays a role in autoimmune disorders such as lupus and psoriasis (18). These confounding factors make it difficult to implement adaptive learning for AMPs.Prior AMP machine-learning studies have focused pri...

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Alpha-Melanocyte Stimulating Hormone: An Emerging Anti-Inflammatory Antimicrobial Peptide

Cited by 56 publications

References 72 publications

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease

Peptide-based imaging agents for cancer detection

Mapping membrane activity in undiscovered peptide sequence space using machine learning

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