NMR Structure Implications of Enhanced Efficacy of Obestatin Fragment Analogs

Krishnarjuna, Bankala; Ganjiwale, Anjali; Manjappara, Uma V.; Raghothama, Srinivasarao

doi:10.1007/s10989-011-9266-8

Cited by 6 publications

(2 citation statements)

References 31 publications

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“…[L4C, I7C]Temporin‐SHf was characterized using NMR spectroscopy in both CD 3 OH and H 2 O/D 2 O solvents. Short linear peptides which do not exhibit structure in water were shown to adopt regular secondary structures in methanol (Hewage, Jiang, Parkinson, Ramage, & Sadler, ; Krishnarjuna, Ganjiwale, Manjappara, & Raghothama, ). Structure evolution in short peptide in methanol is possible due to lower tendency of methanol to participate in hydrogen bonding which may promote internal hydrogen bonding and structure formation in the peptide.…”

Section: Resultsmentioning

confidence: 99%

Disulfide engineering on temporin‐SHf: Stabilizing the bioactive conformation of an ultra‐short antimicrobial peptide

et al. 2019

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In Silico searching for short antimicrobial peptides has revealed temporin‐SHf as the short (8AA), hydrophobic, broad spectrum, and natural antimicrobial peptide. Important drawback associated with temporin‐SHf is the susceptibility of its bioactive conformation for denaturation and proteolytic degradation. In the current report, disulfide engineering strategy has been adopted to improve the stability of bioactive conformation of temporin‐SHf. The functionally non‐critical Leu4 and Ile7 residues at i and i + 3 position of helical conformation of temporin‐SHf were mutated with cysteine disulfide. Designed [L4C, I7C]temporin‐SHf was synthesized, characterized using NMR spectroscopy, and accessed for antimicrobial activity. [L4C, I7C]Temporin‐SHf adopts helical conformation from Phe3 to Phe8 in the absence of membrane‐mimetic environment and retains broad spectrum antimicrobial activity. The reduction potential of cysteine disulfide of [L4C, I7C]temporin‐SHf is −289 mV. Trypsin‐induced digestion and serum‐induced digestion have confirmed the advantage of cysteine disulfide in imparting proteolytic stability to temporin‐SHf. Disulfide‐stabilized temporin‐SHf may serve as a good model for the rational design of temporin‐SHf based antibiotics for treatment of infectious diseases.

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Section: Resultsmentioning

confidence: 99%

Disulfide engineering on temporin‐SHf: Stabilizing the bioactive conformation of an ultra‐short antimicrobial peptide

et al. 2019

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“…The N-terminal (Arg1-Ile3) and C-terminal (Gly16-Ala19) regions, and the Val9-Ala11 region between the turn and the helix, are less well defined. NOEs between the Ile13 amide proton and the Pro12 δ protons were observed, indicating that the proline is acting as a helix inducer rather than a helix breaker [ 25 , 26 ]. The inter-residue NOEs between the Ala11 Hα and Pro12 Hδ resonances are diagnostic of a trans conformation of the peptide bond between Ala11 and Pro12 ( Figure 4 A,B).…”

Section: Resultsmentioning

confidence: 99%

Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins

et al. 2023

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Elevenins are peptides found in a range of organisms, including arthropods, annelids, nematodes, and molluscs. They consist of 17 to 19 amino acid residues with a single conserved disulfide bond. The subject of this study, elevenin‑Vc1, was first identified in the venom of the cone snail Conus victoriae (Gen. Comp. Endocrinol. 2017, 244, 11–18). Although numerous elevenin sequences have been reported, their physiological function is unclear, and no structural information is available. Upon intracranial injection in mice, elevenin-Vc1 induced hyperactivity at doses of 5 or 10 nmol. The structure of elevenin‑Vc1, determined using nuclear magnetic resonance spectroscopy, consists of a short helix and a bend region stabilised by the single disulfide bond. The elevenin-Vc1 structural fold is similar to that of α‑conotoxins such as α‑RgIA and α‑ImI, which are also found in the venoms of cone snails and are antagonists at specific subtypes of nicotinic acetylcholine receptors (nAChRs). In an attempt to mimic the functional motif, Asp‑Pro‑Arg, of α‑RgIA and α‑ImI, we synthesised an analogue, designated elevenin‑Vc1‑DPR. However, neither elevenin-Vc1 nor the analogue was active at six different human nAChR subtypes (α1β1εδ, α3β2, α3β4, α4β2, α7, and α9α10) at 1 µM concentrations.

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Peptide Toxin Structure and Function by NMR

Norton

2017

Modern Magnetic Resonance

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NMR Structure Implications of Enhanced Efficacy of Obestatin Fragment Analogs

Cited by 6 publications

References 31 publications

Disulfide engineering on temporin‐SHf: Stabilizing the bioactive conformation of an ultra‐short antimicrobial peptide

Disulfide engineering on temporin‐SHf: Stabilizing the bioactive conformation of an ultra‐short antimicrobial peptide

Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins

Peptide Toxin Structure and Function by NMR

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