Polypeptide Chains Containing<scp>d</scp>-γ-Hydroxyvaline

Pisarewicz, Katarzyna; Mora, D. Gonzalez; Pflueger, Fred; Fields, Gregg B.; Marí, Frank

doi:10.1021/ja050088m

Cited by 92 publications

(52 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Conotoxins are small peptides, mostly 10-40 amino acid residues in length. However the shortest conotoxin, conophanmus-V [20], has 8 amino acid residues and the longest conopeptide, con-ikot-ikot, is reported to have 86 amino acid residues [21]. The molecular weight of conopeptides ranges from 847 Da -9445 Da and their isoelectric point shows variation, from very acidic to basic.…”

Section: Sequence Of Conotoxinsmentioning

confidence: 99%

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Mir¹,

Karim²,

Kamal³

et al. 2016

CPD

View full text Add to dashboard Cite

Cone snails, also known as marine gastropods, from Conus genus produce in their venom a diverse range of small pharmacologically active structured peptides called conotoxins. The cone snail venoms are widely unexplored arsenal of toxins with therapeutic and pharmacological potential, making them a treasure trove of ligands and peptidic drug leads. Conotoxins are small disulphide bonded peptides which act as remarkable selective inhibitors and modulators of ion channels (calcium, sodium, potassium), nicotinic acetylcholine receptors, noradrenaline transporters, N-methyl-D-aspartate receptors, and neurotensin receptors. They are highly potent and specific against several neuronal targets making them valuable as research tools, drug leads and even therapeutics. In this review we discuss their gene superfamily classification, nomenclature, post-translational modification, structural framework, pharmacology and medical applications of the active conopeptides. We aim to give an overview of their structure and therapeutic potential. Understanding these aspects of conopeptides will help in designing more specific peptidic analogues.

show abstract

Section: Sequence Of Conotoxinsmentioning

confidence: 99%

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Mir¹,

Karim²,

Kamal³

et al. 2016

CPD

View full text Add to dashboard Cite

show abstract

“…Essentially, the introduction of D-amino acids in a peptide aids to design substrates that are bacterial species specific due to their presence as a component of the bacterial cell wall (43). In contrast, D-amino acids are, with only a few exceptions, not metabolized in eukaryotic cells (33) In our view, this approach has opened a novel, attractive avenue to develop more bacterial species-specific substrates that can be applied in the diagnosis of infectious agents in complex matrices. Based on the study on D-amino-acid-containing peptides for the detection of Bacillus spp., we developed a substrate library containing fluorogenic dipeptides that contain no, one, or two D-amino acids.…”

mentioning

confidence: 99%

Highly Specific Protease-Based Approach for Detection of Porphyromonas gingivalis in Diagnosis of Periodontitis

et al. 2012

View full text Add to dashboard Cite

Porphyromonas gingivalis is associated with the development of periodontitis. Here we describe the development of a highly specific protease-based diagnostic method for the detection of P. gingivalis in gingival crevicular fluid. Screening of a proteolytic peptide substrate library, including fluorogenic dipeptides that contain D-amino acids, led to the discovery of five P. gingivalisspecific substrates. Due to the presence of lysine and arginine residues in these substrates, it was hypothesized that the cleavage was mediated by the gingipains, a group of P. gingivalis-specific proteases. This hypothesis was confirmed by the observation that P. gingivalis gingipain knockout strains demonstrated clearly impaired substrate cleavage efficacy. Further, proteolytic activity on the substrates was increased by the addition of the gingipain stimulators dithiothreitol and L-cysteine and decreased by the inhibitors leupeptin and N-ethylmaleimide. Screening of saliva and gingival crevicular fluid of periodontitis patients and healthy controls showed the potential of the substrates to diagnose the presence of P. gingivalis proteases. By using paper points, a sensitivity of approximately 10 5 CFU/ml was achieved. P. gingivalis-reactive substrates fully composed of L-amino acids and Bz-L-Arg-NHPhNO 2 showed a relatively low specificity (44 to 85%). However, the five P. gingivalis-specific substrates that each contained a single D-amino acid showed high specificity (96 to 100%). This observation underlines the importance of the presence of D-amino acids in substrates used for the detection of bacterial proteases. We envisage that these substrates may improve the specificity of the current enzyme-based diagnosis of periodontitis associated with P. gingivalis.

show abstract

“…4). Posttranslational modifications in Conus generally aid in stabilizing the peptide structure (5,6) as well as varying the structure and shape of the peptide to optimize target binding (7)(8)(9).…”

mentioning

confidence: 99%

Identification of Conus Peptidylprolyl Cis-Trans Isomerases (PPIases) and Assessment of Their Role in the Oxidative Folding of Conotoxins

Safavi-Hemami

Bułaj

Olivera

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Peptidylprolyl cis-trans isomerases (PPIases) are ubiquitous proteins that catalyze the cis-trans isomerization of prolines. A number of proteins, such as Drosophila rhodopsin and the human immunodeficiency viral protein HIV-1 Gag, have been identified as endogenous substrates for PPIases. However, very little is known about the interaction of PPIases with small, disulfide-rich peptides. Marine cone snails synthesize a wide array of cysteine-rich peptides, called conotoxins, many of which contain one or more prolines or hydroxyprolines. To identify whether PPIase-associated cis-trans isomerization of these residues affects the oxidative folding of conotoxins, we identified, sequenced, and expressed three functionally active isoforms of PPIase from the venom gland of Conus novaehollandiae, and we characterized their ability to facilitate oxidative folding of conotoxins in vitro. Three conotoxins, namely -GIIIA, -SIIIA, and -MVIIC, derived from two distinct toxin gene families were assayed. Conus PPIase significantly increased the rate of appearance of the native form of -GIIIA, a peptide containing three hydroxyprolines. In contrast, the presence of PPIase had no effect on the folding of -SIIIA and -MVIIC, peptides containing no or one proline residue, respectively. We further showed that an endoplasmic reticulum-resident PPIase isoform facilitated folding of -GIIIA more efficiently than two cytosolic isoforms. This is the first study to demonstrate PPIase-assisted folding of conotoxins, small disulfide-rich peptides with unique structural properties.

show abstract

Polypeptide Chains Containingd-γ-Hydroxyvaline

Cited by 92 publications

References 62 publications

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Highly Specific Protease-Based Approach for Detection of Porphyromonas gingivalis in Diagnosis of Periodontitis

Identification of Conus Peptidylprolyl Cis-Trans Isomerases (PPIases) and Assessment of Their Role in the Oxidative Folding of Conotoxins

Contact Info

Product

Resources

About