Proline-Dependent Structural and Biological Properties of Peptides and Proteins

Yaron, Avraham; Naider, Fred

doi:10.3109/10409239309082572

Cited by 535 publications

(355 citation statements)

References 30 publications

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“…It was also found that IPP and LKP are resistant to metabolism by liver enzymes, suggesting that the tripeptides will not be degraded during first pass metabolism and will be transported into systemic circulation intact. The presence of proline moieties in these tripeptides seem to provide inherent resistance to enzymatic degradation (35,36), so the stability results are in keeping with that.…”

Section: Discussionmentioning

confidence: 64%

Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

et al. 2015

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Publication information Peptides, 71 : 1-7Publisher Elsevier Item record/more information http://hdl.handle.net/10197/8723 Publisher's statementThis is the author's version of a work that was accepted for publication in Peptides. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Peptides (VOL 71, ISSUE 2015, (2015 colonic mucosae were low, but were significantly increased in each tissue type by the medium chain fatty acids (MCFA) permeation enhancers, sodium caprate (C 10 ) and the sodium salt of 10-undecylenic acid (uC 11 ). IPP and LKP were therefore stable against intestinal and liver peptidases and were non-cytotoxic; their P app values across rat intestinal mucosae were low, but could be increased by MCFA. There is potential to make on oral dosage form once in vivo pharmacology is confirmed.

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Section: Discussionmentioning

confidence: 64%

Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

et al. 2015

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“…Due to their cyclic structure, proline residues bestow unique conformational constraints on polypeptide chain structure, affecting the susceptibility of proximal peptide bonds to proteolytic cleavage (Yaron & Naider, 1993). Therefore, for the cleavage of Pro-Xaa peptide bonds (where Xaa is any amino acid) a specialised group of proteases, the prolyl peptidases, have evolved and their activity in vivo may have important physiological significance (Rosenblum & Kozarich, 2003).…”

Section: Discussionmentioning

confidence: 99%

Purification, identification and characterisation of seprase from bovine serum

Collins

McMahon

O’Brien

et al. 2004

The International Journal of Biochemistry & Cell Biology

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ABBREVIATIONSAMC, 7-amino-4-methylcoumarin; BCA, bicinchoninic acid; CPC, calcium phosphate cellulose; DFP, diisopropylfluorophosphate; FPLC, fast protein liquid chromatography; HIC, hydrophobic interaction chromatography; PO, prolyl oligopeptidase; TFA, trifluoroacetic acid; Z, N-benzyloxycarbonyl; ZIP, Z-Pro-prolinal-insensitive Z-Gly-Pro-AMC-hydrolysing peptidase. ABSTRACTThe study and identification for the first time of a soluble form of a Seprase activity from bovine serum is presented. To date, this activity has only been reported to be an integral membrane protease but has been known to shed from its membrane. The activity was purified 30,197-fold to homogeneity, using a combination of column chromatographies, from bovine serum. Inhibition by DFP, resulting in an IC 50 of 100nM confirms classification as a serine protease. The protease after separation and visualisation by native PAGE was subjected to tryptic digestion and the subsequent peptides sequenced. Each peptide sequenced was found to be present in the primary structure of Seprase/Fibroblast Activation Protein (FAP), a serine gelatinase specific for proline-containing peptides and macromolecules. Substrate specificity studies using kinetic, RP-HPLC and LC-MS analysis of synthetic peptides suggest that this peptidase has an extended substrate-binding region in addition to the primary specificity site S 1 . This analysis revealed at least five subsites to be involved in enzyme-substrate binding, 2 with the smallest peptide cleaved being a tetrapeptide. A proline residue in position P 1 was absolutely necessary therefore showing high primary substrate specificity for the Pro-X bond, while a preference for a hydrophobic residue at the C-terminal end of the scissile bond (P 1 ʹ′) was evident. The enzyme also showed complete insensitivity to the prolyl oligopeptidase specific inhibitors, JTP-4819, Fmoc-Ala-pyrrCN and Z-Phe-Pro-BT. To date, no physiological substrate has clearly been defined for this protease but its ability to effectively degrade gelatin suggests a candidate protein substrate in vivo and a possible role in extracellular matrix protein degradation.

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“…[1][2][3][4][5][6][7][8][9]. In addition, its w torsion angle is commonly found either in the right-handed 3 10 -/a-helical region (230 to 2508, or cis 0 conformation) or in the left-handed, semi-extended, region [2150 ± 108, or trans 0 , or poly-(L-Pro) n conformation].…”

Section: Introductionmentioning

confidence: 99%

C^α‐Methyl proline: A unique example of split personality

et al. 2007

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Methylation at the Cα‐position of a Pro residue was expected to lock the preceding tertiary amide (ω) torsion angle of the resulting (αMe)Pro to the trans disposition and to restrict the ϕ,ψ surface to the single region where the 310/α‐helices are found (in this five‐membered ring residue ϕ is severely constrained to about ±65° by its cyclic nature). The results of the present X‐ray diffraction work on a selected set of four Nα‐blocked, (αMe)Pro‐containing, dipeptide N′‐alkylamides clearly show that, although the region of the conformational map largely preferred by (αMe)Pro would indeed be that typical of 310/α‐helices, the semi‐extended [type‐II poly(Pro)n helix] region can also be explored by this extremely sterically demanding Cα‐tetrasubstituted α‐amino acid. In addition, the known high propensity for β‐turn formation of the Pro residue is further enhanced in peptides based on its Cα‐methylated derivative. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 465–470, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Proline-Dependent Structural and Biological Properties of Peptides and Proteins

Cited by 535 publications

References 30 publications

Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

Purification, identification and characterisation of seprase from bovine serum

C^α‐Methyl proline: A unique example of split personality

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Proline-Dependent Structural and Biological Properties of Peptides and Proteins

Cited by 535 publications

References 30 publications

Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

Purification, identification and characterisation of seprase from bovine serum

Cα‐Methyl proline: A unique example of split personality

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Product

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C^α‐Methyl proline: A unique example of split personality