Cycloquest: identification of cyclopeptides via database search of their mass spectra against genome databases.

Hundreds of ribosomally synthesized cyclopeptides have been isolated from all domains of life, the vast majority having been reported in the last 15 years. Studies of cyclic peptides have highlighted their exceptional potential both as stable drug scaffolds and as biomedicines in their own right. Despite this, computational techniques for cyclopeptide identification are still in their infancy, with many such peptides remaining uncharacterized. Tandem mass spectrometry has occupied a niche role in cyclopeptide identification, taking over from traditional techniques such as nuclear magnetic resonance spectroscopy (NMR). MS/MS studies require only picogram quantities of peptide (compared to milligrams for NMR studies) and are applicable to complex samples, abolishing the requirement for time-consuming chromatographic purification. While database search tools such as Sequest and Mascot have become standard tools for the MS/MS identification of linear peptides, they are not applicable to cyclopeptides, due to the parent mass shift resulting from cyclization and different fragmentation patterns of cyclic peptides. In this paper, we describe the development of a novel database search methodology to aid in the identification of cyclopeptides by mass spectrometry and evaluate its utility in identifying two peptide rings from Helianthus annuus, a bacterial cannibalism factor from Bacillus subtilis, and a θ-defensin from Rhesus macaque.

[1]  Susana P. Gaudêncio,et al.  Multiplex de novo sequencing of peptide antibiotics. , 2011, Journal of computational biology : a journal of computational molecular cell biology.

[2]  Hosein Mohimani,et al.  Sequencing cyclic peptides by multistage mass spectrometry , 2011, Proteomics.

[3]  D. Craik,et al.  Albumins and their processing machinery are hijacked for cyclic peptides in sunflower. , 2011, Nature chemical biology.

[4]  J. Vederas,et al.  [Drug discovery and natural products: end of era or an endless frontier?]. , 2011, Biomeditsinskaia khimiia.

[5]  W. A. van der Donk,et al.  Genome mining for ribosomally synthesized natural products. , 2011, Current opinion in chemical biology.

[6]  Pavel A Pevzner,et al.  Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of Bacillus subtilis , 2010, Proceedings of the National Academy of Sciences.

[7]  D. Russell,et al.  High-throughput method for on-target performic acid oxidation of MALDI-deposited samples. , 2010, Journal of mass spectrometry : JMS.

[8]  D. Craik,et al.  A new "era" for cyclotide sequencing. , 2010, Biopolymers.

[9]  Nuno Bandeira,et al.  Dereplication and De Novo Sequencing of Nonribosomal Peptides , 2009, Nature Methods.

[10]  J. Clements,et al.  Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4. , 2009, Chemistry & biology.

[11]  A. Waring,et al.  Reawakening Retrocyclins: Ancestral Human Defensins Active Against HIV-1 , 2009, PLoS biology.

[12]  Ari M Frank,et al.  A ranking-based scoring function for peptide-spectrum matches. , 2009, Journal of proteome research.

[13]  P. Pevzner,et al.  Spectral Dictionaries , 2009, Molecular & Cellular Proteomics.

[14]  Sylvie Garneau-Tsodikova,et al.  Isolation and Characterization of Carnocyclin A, a Novel Circular Bacteriocin Produced by Carnobacterium maltaromaticum UAL307 , 2008, Applied and Environmental Microbiology.

[15]  Pavel A Pevzner,et al.  Algorithm for identification of fusion proteins via mass spectrometry. , 2008, Journal of proteome research.

[16]  Richard D. Smith,et al.  Whole proteome analysis of post-translational modifications: applications of mass-spectrometry for proteogenomic annotation. , 2007, Genome research.

[17]  J. Tagg,et al.  Uberolysin: a novel cyclic bacteriocin produced by Streptococcus uberis. , 2007, Microbiology.

[18]  R. Dickson,et al.  Design and synthesis of redox stable analogues of sunflower trypsin inhibitors (SFTI-1) on solid support, potent inhibitors of matriptase. , 2007, Organic letters.

[19]  Jason P. Mulvenna,et al.  CyBase: a database of cyclic protein sequence and structure , 2005, Nucleic Acids Res..

[20]  Pavel A. Pevzner,et al.  Peptide sequence tags for fast database search in mass-spectrometry. , 2005 .

[21]  P. Pevzner,et al.  InsPecT: identification of posttranslationally modified peptides from tandem mass spectra. , 2005, Analytical chemistry.

[22]  Y. Suketa,et al.  Chemical structure of circulin B , 1965, Experientia.

[23]  Y. Suketa,et al.  Chemical structure of circulin A , 2005, Experientia.

[24]  R. Losick,et al.  Cannibalism by Sporulating Bacteria , 2003, Science.

[25]  J. Vederas,et al.  Structure of subtilosin A, an antimicrobial peptide from Bacillus subtilis with unusual posttranslational modifications linking cysteine sulfurs to alpha-carbons of phenylalanine and threonine. , 2003, Journal of the American Chemical Society.

[26]  I. Enyedy,et al.  Synthesis and evaluation of the sunflower derived trypsin inhibitor as a potent inhibitor of the type II transmembrane serine protease, matriptase. , 2001, Bioorganic & medicinal chemistry letters.

[27]  D. N. Perkins,et al.  Probability‐based protein identification by searching sequence databases using mass spectrometry data , 1999, Electrophoresis.

[28]  Jun Yuan,et al.  A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. , 1999, Science.

[29]  S Luckett,et al.  High-resolution structure of a potent, cyclic proteinase inhibitor from sunflower seeds. , 1999, Journal of molecular biology.

[30]  I. Campbell,et al.  Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1. , 1995, Biochemistry.

[31]  M. Wilm,et al.  Error-tolerant identification of peptides in sequence databases by peptide sequence tags. , 1994, Analytical chemistry.

[32]  P. Anderson,et al.  Cyclopsychotride A, a biologically active, 31-residue cyclic peptide isolated from Psychotria longipes. , 1994, Journal of natural products.

[33]  J. Yates,et al.  An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database , 1994, Journal of the American Society for Mass Spectrometry.

[34]  L. Pannell,et al.  Circulins A and B. Novel human immunodeficiency virus (HIV)-inhibitory macrocyclic peptides from the tropical tree Chassalia parvifolia. , 1994 .

[35]  R. Farías,et al.  Microcin 25, a novel antimicrobial peptide produced by Escherichia coli , 1992, Journal of bacteriology.

[36]  T. Takao,et al.  Subtilosin A, a new antibiotic peptide produced by Bacillus subtilis 168: isolation, structural analysis, and biogenesis. , 1985, Journal of biochemistry.

[37]  H. Faulstich,et al.  Virotoxins: actin-binding cyclic peptides of Amanita virosa mushrooms. , 1980, Biochemistry.

[38]  L. Gran,et al.  On the effect of a polypeptide isolated from "Kalata-Kalata" (Oldenlandia affinis DC) on the oestrogen dominated uterus. , 2009, Acta pharmacologica et toxicologica.

[39]  T. Wieland,et al.  Poisonous principles of mushrooms of the genus Amanita. Four-carbon amines acting on the central nervous system and cell-destroying cyclic peptides are produced. , 1968, Science.