A Novel Anti-HIV Macrocyclic Peptide from Palicourea condensata

Bokesch, Heidi R.; Pannell, Lewis K.; Cochran, Pamela K.; Sowder, Raymond C.; McKee, Tawnya C.; Boyd, Michael R.

doi:10.1021/np000372l

Cited by 138 publications

(107 citation statements)

References 14 publications

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“…Cyclotides can also be found in plants of a second family, namely the Rubiaceae. However, for this family the literature seems to suggest that in some species cyclotides are only expressed in woody parts, such as the bark (Gustafson et al, 1994;Bokesch et al, 2001).…”

Section: Discussion Cyclotide Expression and Biosynthesismentioning

confidence: 99%

Tissue-Specific Expression of Head-to-Tail Cyclized Miniproteins in Violaceae and Structure Determination of the Root CyclotideViola hederacearoot cyclotide1[W]

2004

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The plant cyclotides are a family of 28 to 37 amino acid miniproteins characterized by their head-to-tail cyclized peptide backbone and six absolutely conserved Cys residues arranged in a cystine knot motif: two disulfide bonds and the connecting backbone segments form a loop that is penetrated by the third disulfide bond. This knotted disulfide arrangement, together with the cyclic peptide backbone, renders the cyclotides extremely stable against enzymatic digest as well as thermal degradation, making them interesting targets for both pharmaceutical and agrochemical applications. We have examined the expression patterns of these fascinating peptides in various Viola species (Violaceae). All tissue types examined contained complex mixtures of cyclotides, with individual profiles differing significantly. We provide evidence for at least 57 novel cyclotides present in a single Viola species (Viola hederacea). Furthermore, we have isolated one cyclotide expressed only in underground parts of V. hederacea and characterized its primary and three-dimensional structure. We propose that cyclotides constitute a new family of plant defense peptides, which might constitute an even larger and, in their biological function, more diverse family than the well-known plant defensins.

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Section: Discussion Cyclotide Expression and Biosynthesismentioning

confidence: 99%

Tissue-Specific Expression of Head-to-Tail Cyclized Miniproteins in Violaceae and Structure Determination of the Root CyclotideViola hederacearoot cyclotide1[W]

2004

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“…Loop 6 is formed at the cyclization point of the linear precursor. References for the listed cyclotides are as follows: cycloviolin C (Hallock et al, 2000), varv A (Claeson et al, 1998), Hypa A (Broussalis et al, 2001), cyclopsychotride (Witherup et al, 1994), circulin A (Derua et al, 1996), palicourein (Bokesch et al, 2001), and kalata B1 (Saether et al, 1995). A ribbon diagram of the cyclotide framework based on the structure of kalata B1 (PDB ID 1NB1) with the cystine knot core rendered and numbering of loops is shown in the middle of the figure.…”

Section: Introductionmentioning

confidence: 99%

A Continent of Plant Defense Peptide Diversity: Cyclotides in AustralianHybanthus(Violaceae)

et al. 2005

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Cyclotides are plant-derived miniproteins that have the unusual features of a head-to-tail cyclized peptide backbone and a knotted arrangement of disulfide bonds. It had been postulated that they might be an especially large family of host defense agents, but this had not yet been tested by field data on cyclotide variation in wild plant populations. In this study, we sampled Australian Hybanthus (Violaceae) to gain an insight into the level of variation within populations, within species, and between species. A wealth of cyclotide diversity was discovered: at least 246 new cyclotides are present in the 11 species sampled, and 26 novel sequences were characterized. A new approach to the discovery of cyclotide sequences was developed based on the identification of a conserved sequence within a signal sequence in cyclotide precursors. The number of cyclotides in the Violaceae is now estimated to be >9000. Cyclotide physicochemical profiles were shown to be a useful taxonomic feature that reflected species and their morphological relationships. The novel sequences provided substantial insight into the tolerance of the cystine knot framework in cyclotides to amino acid substitutions and will facilitate protein engineering applications of this framework.

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“…It was found that both peptides exhibited IC 50 values that were 5.0 μM when directed against cell lines of lymphoma (U-937 GTB) colorectal cancer (Ht116) and colonadeno carcinoma (HT29) that were generally comparable to that of doxorubicin [62,63], a well-established anticancer drug [64]. Other AHDPs from plants of the Rubiaceae, include palicourein (net charge -1), from the tropical plant, Palicourea condensate [65], and chaC1 (net charge -1), which was recently discovered in Chassalia chartacea [66]. These peptides were found to have potent activity against cell lines of cervical cancer (HeLa) and acute lymphoblastic leukaemia (CEM-SS) with IC 50 values of 1.5 μM and 9.8 μM, respectively [66,67].…”

Section: Ahdps From Cyclotidesmentioning

confidence: 99%

“…However, based on structural differences in their molecular framework, cyclotides can be divided into a number of groups [41,42], including two major subfamilies, generally known as the Möbius and bracelet peptides (Fig. 4) [15,77], and a much smaller group termed chimeric cyclotides [65]. The Möbius and bracelet subfamilies have fundamentally different molecular architectures that are primarily distinguished by the presence of a conserved proline residue in cis conformation in loop 5 of the former subfamily, causing a 180° twist in the loop, which is not seen in the latter subfamily [15,77].…”

Section: Ahdps From Cyclotidesmentioning

confidence: 99%

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Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action

Harris¹,

Prabhu²,

Dennison³

et al. 2016

PPL

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Abstract:It is becoming increasingly clear that plants ranging across the plant kingdom produce anionic host defence peptides (AHDPs) with potent activity against a wide variety of human cancers cells. In general, this activity involves membrane partitioning by AHDPs, which leads to membranolysis and / or internalization to attack intracellular targets such as DNA. Several models have been proposed to describe these events including: the toroidal pore and Shai-Matsuzaki-Huang mechanisms but, in general, the mechanisms underpinning the membrane interactions and anticancer activity of these peptides are poorly understood. Plant AHDPs with anticancer activity can be conveniently discussed with reference to two groups: cyclotides, which possess cyclic molecules stabilized by cysteine knot motifs, and other ADHPs that adopt extended andhelical conformations. Here, we review research into the anticancer action of these two groups of peptides along with current understanding of the mechanisms underpinning this action.

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A Novel Anti-HIV Macrocyclic Peptide from Palicourea condensata

Cited by 138 publications

References 14 publications

Tissue-Specific Expression of Head-to-Tail Cyclized Miniproteins in Violaceae and Structure Determination of the Root CyclotideViola hederacearoot cyclotide1[W]

Tissue-Specific Expression of Head-to-Tail Cyclized Miniproteins in Violaceae and Structure Determination of the Root CyclotideViola hederacearoot cyclotide1[W]

A Continent of Plant Defense Peptide Diversity: Cyclotides in AustralianHybanthus(Violaceae)

Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action

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