title: Chemical Crosslinking: Role in Protein and Peptide Science.
abstract: BACKGROUND
  Chemical crosslinking refers to intermolecular or intramolecular joining of two or more molecules by a covalent bond. The reagents that are used for the purpose are referred to as 'crosslinking reagents' or 'crosslinkers'. Based on factors like reactivity and spacer length these are classified into different types, each having its own specific function and application. In recent times, chemical crosslinking has emerged as an efficient tool for the study of biomolecules like proteins. It finds its application in various studies including the attachment of proteins to a solid support for the study of membrane receptors, protein-protein complexes, protein-DNA complexes, and others. When coupled with techniques like mass spectroscopy, it has been used not only for the determination of three dimensional structures of proteins but also for the study of protein-protein interactions and determination of interesting sites. This combination of mass spectrometry techniques and bioinformatics, added yet another dimension to our present day understanding of protein chemistry. Thus, chemical crosslinking has multitude uses that it can be put to.
  
  
  METHODS
  We undertook a systematic search of bibliographic databases and search engine such as Google Scholar, Scifinder, Scopus, Mendeley etc for review of research literature. We excluded research paper which only reported synthesis of crosslinker molecules and did not involve any mass spectrometry studies.
  
  
  RESULTS
  Sixty-four papers were included in the review. The majority of references were taken from last ten years as there has been an immense progress in this area in the recent years. Eleven classical papers in this field were included which talk about basic of this methodology. Thirty-two papers discussed about various types of organic groups used for designing chemical cross-linkers and various methodologies which were used to enhance the crosslinking efficiency. These papers also highlight various strategies used to enhance detection of cross-linked proteins and various computer software used to detect cross-linking sites from mass data. Twenty-one papers showed the proof concept application of this methodology to detect protein crosslinking in-vivo and in-vitro.
  
  
  CONCLUSIONS
  The findings of this review confirm the importance chemical crosslinking combined with mass spectroscopy as a low cost alternative to understand protein-protein interaction. The information generated by this methodology can help in better understating of various diseases and for the development of better drugs for them.
authors.affiliation: Department of Applied Science, The Northcap University, Sector 23A, Gurgaon, Haryana 122017, India.
authors.forename: Bharti
authors.initials: B
authors.lastname: Arora
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110 007, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Tandon
authors.affiliation: Graduate School of Information Science and Electrical Engineering, Kyushu University, Fukuoka 819-0395, Japan.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Attri
authors.affiliation: Division of sustainable chemistry, Rudraksh Proudhyogiki Sangathan Delhi-110092, India.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhatia
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D010455:Peptides / Q000737:chemistry*; D066329:Protein Aggregates; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012984:Software
chemical_list: D003432:Cross-Linking Reagents; D010455:Peptides; D066329:Protein Aggregates; D011506:Proteins
keywords: Bottom-up approach; crosslinker; mass spectroscopy; software; structural biology; top-down approach