Cyclopsychotride A, a Biologically Active, 31-Residue Cyclic Peptide Isolated from Psychotria longipes

Witherup, Keith M.; Bogusky, Michael J.; Anderson, Paul S.; Ramjit, Harri G.; Ransom, Richard W.; Wood, Theresa; Sardana, Mohinder K.

doi:10.1021/np50114a002

Cited by 237 publications

(249 citation statements)

References 4 publications

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“…Of particular interest among naturally occurring examples have been a series of plant-derived proteins referred to as the cyclotides (1). These include kalata B1 (2), the circulins (3), cyclopsychotride (4), and several peptides from Viola species (5-7). The cyclotides comprise 29-31 amino acids, including six highly conserved Cys residues that form a cystine knot (8)(9).…”

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confidence: 99%

“…For example, in 1970, kalata B1was reported as the active ingredient in a tea used by women in the Congo region of Africa to accelerate childbirth (16,17), although it was some 25 years later before the sequence and cyclic nature of the peptide were determined (2). The circulins were discovered in screens focusing on anti-HIV activity (3), cyclopsychotride for inhibition of neurotensin binding (4), and various Viola peptides for hemolytic activity (7). Thus, all of the known macrocyclic peptides have diverse biological activities, but their function in plants was not known.…”

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confidence: 99%

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Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis

Jennings

West

Waine

et al. 2001

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

488

679

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Several members of the Rubiaceae and Violaceae families produce a series of cyclotides or macrocyclic peptides of 29 -31 amino acids with an embedded cystine knot. We aim to understand the mechanism of synthesis of cyclic peptides in plants and have isolated a cDNA clone that encodes the cyclotide kalata B1 as well as three other clones for related cyclotides from the African plant Oldenlandia affinis. The cDNA clones encode prepropeptides with a 20-aa signal sequence, an N-terminal prosequence of 46 -68 amino acids and one, two, or three cyclotide domains separated by regions of about 25 aa. The corresponding cyclotides have been isolated from plant material, indicating that the cyclotide domains are excised and cyclized from all four predicted precursor proteins. The exact processing site is likely to lie on the N-terminal side of the strongly conserved GlyLeuPro or SerLeuPro sequence that flanks both sides of the cyclotide domain. Cyclotides have previously been assigned an antimicrobial function; here we describe a potent inhibitory effect on the growth and development of larvae from the Lepidopteran species Helicoverpa punctigera.

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Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis

Jennings

West

Waine

et al. 2001

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

488

679

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“…[4] It is believed that the compact CCK motif of cyclotides is responsible for their exceptional resistance against chemical, thermal, and proteolytic degradation. [5] Cyclotides display a diverse range of biological activities, including uterotonic, [6] haemolytic, [7][8][9] neurotensin antagonistic, [10] HIV inhibitory, [11] antimicrobial, [12] cytotoxic, [13] antifouling, [14] and trypsin inhibitory activities. [15] In addition, kalata B1 and B2 have been shown to inhibit the growth and development of Helicoverpa punctigera and H. armigera larvae, suggesting that cyclotides function as insecticidal agents as part of plant defence systems.…”

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Structure and Activity of the Leaf-Specific Cyclotide vhl-2

et al. 2010

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Cyclotides are plant-derived macrocyclic peptides with potential applications in the pharmaceutical and agricultural industries. In addition to their presumed natural function as host-defence peptides arising from their insecticidal activity, their other biological activities include antimicrobial, haemolytic, and cytotoxic activities, but at present, only limited information is available on the structural and chemical features that are important for these various activities. In the current study, we determined the three-dimensional structure of vhl-2, a leaf-specific cyclotide. Although the characteristic cyclic cystine knot fold of other cyclotides is maintained in vhl-2, it has more potent haemolytic activity than well-characterized cyclotides such as kalata B1 and kalata B8. Analysis of surface hydrophobicity and haemolytic activity for a range of cyclotides indicates a correlation between them, with increasing hydrophobicity resulting in increased haemolytic activity. This correlation is consistent with membrane binding being a vital step in mediating the various cytotoxic activities of cyclotides. The gene sequence for vhl-2 was determined and indicates that vhl-2 is processed from a multidomain precursor protein that also encodes the cyclotide cycloviolacin H3.

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“…These peptides display an interesting range of biological activities, which led to their initial discovery. The circulins were found in a screen for anti-human immunodeficiency virus activity (8), cyclopsychotride A inhibits neurotensin binding to cell membranes (9), and kalata B1 shows uterotonic activity (6,10). Violapeptide I (11) was originally discovered based on its hemolytic activity, and it has recently been shown that kalata B1 (12,13), the circulins (12,13), and cyclopsychotride A (13) also have relatively weak hemolytic activity.…”

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Acyclic Permutants of Naturally Occurring Cyclic Proteins

Daly

Craik

2000

Journal of Biological Chemistry

104

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Kalata B1 is a prototypic member of the unique cyclotide family of macrocyclic polypeptides in which the major structural features are a circular peptide backbone, a triple-stranded ␤-sheet, and a cystine knot arrangement of three disulfide bonds. The cyclotides are the only naturally occurring family of circular proteins and have prompted us to explore the concept of acyclic permutation, i.e. opening the backbone of a cross-linked circular protein in topologically permuted ways. We have synthesized the complete suite of acyclic permutants of kalata B1 and examined the effect of acyclic permutation on structure and activity. Only two of six topologically distinct backbone loops are critical for folding into the native conformation, and these involve disruption of the embedded ring in the cystine knot. Surprisingly, it is possible to disrupt regions of the ␤-sheet and still allow folding into native-like structure, provided the cystine knot is intact. Kalata B1 has mild hemolytic activity, but despite the overall structure of the native peptide being retained in all but two cases, none of the acyclic permutants displayed hemolytic activity. This loss of activity is not localized to one particular region and suggests that cyclization is critical for hemolytic activity.

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Cyclopsychotride A, a Biologically Active, 31-Residue Cyclic Peptide Isolated from Psychotria longipes

Cited by 237 publications

References 4 publications

Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis

Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis

Structure and Activity of the Leaf-Specific Cyclotide vhl-2

Acyclic Permutants of Naturally Occurring Cyclic Proteins

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