title: Pregnancy-Specific β1-Glycoproteins: Combined Biomarker Roles, Structure/Function Relationships and Implications for Drug Design.
abstract: BACKGROUND
  Pregnancy specific β1-glycoproteins (PSGs) have long been recognized as trophoblast quality and embryo viability markers. However, biological roles of PSGs remain obscure, and structure/function relationships to other feto-placental proteins as well as implications for drug design have not been reviewed. This review summarizes and discusses advances in 45-year studies of PSGs with focus on the latest achievements and the challenges for future investigations.
  
  
  METHODS
  Literature search was performed to review the majority of recent PSG studies with emphasis on usage of high-throughput integrated proteomic profiling technologies, systems biology and bioinformatics approaches that enhance novel biomarker and drug target discovery as well as protein structure/activity analysis.
  
  
  RESULTS
  Clinical significance and screening performance improved when PSG measurements were combined with those of other placenta-derived proteins: hCG, hPL, PAPP-A, and proMBP. Nevertheless, analysis of protein co-expression and co-localization data and the involvement of PSGs in protein interaction networks are being introduced to discover novel, specific and high-sensitive, gestational/cancer biomarkers. Despite biological roles of PSGs are not fully understood, there are evidences of that they exhibit immunomodulatory, antiinflammatory and proangiogenic effects. Investigation of structure/function relationships showed that PSGs may function in cooperative/coordinated manner with numerous regulatory proteins including alpha-fetoprotein and transforming growth factors-β; this is provided by the presence of conserved short linear motifs (SLiMs) such as RGD, PXXP and AFP14-20-like (YXCX) ones.
  
  
  CONCLUSIONS
  PSG-derived peptides may be used as a rationale to design novel drugs that mimic SLiMs involved in protein-protein interactions to inhibit domain-motif binding and to block cell signaling, and/or exert immunomodulatory, anti-inflammatory and proangiogenic effects.
authors.forename: Nurbubu T
authors.initials: NT
authors.lastname: Moldogazieva
authors.forename: Innokenty M
authors.initials: IM
authors.lastname: Mokhosoev
authors.affiliation: Department of Biochemistry and Molecular Biology, N.I. Pirogov Russian National Research Medical University, 1 Ostrovityanov street, 117997 Moscow, Russian Federation.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Terentiev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D040901:Proteomics; D013329:Structure-Activity Relationship
chemical_list: D015415:Biomarkers; D011268:Pregnancy-Specific beta 1-Glycoproteins
keywords: Pregnancy-specific beta1-glycoproteins; biomarker profiling; embryonic/placental development; novel drug design; short linear motifs; structure/function relationships; trophoblastic
  diseases