Rational design of antibodies targeting specific epitopes within intrinsically disordered proteins

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 32, 2015, Pages 9902-9907

  Sormanni, Pietro ^a   Aprile, Francesco A ^a   Vendruscolo, Michele ^a   Tessier, Peter M ^b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b RENSSELAER POLYTECHNIC INSTITUTE   (United States)

Author keywords

Complementary peptides; Protein aggregation; Protein design

Indexed keywords

ALPHA SYNUCLEIN; AMYLIN; AMYLOID BETA PROTEIN[1-42]; EPITOPE; INTRINSICALLY DISORDERED PROTEIN; NANOBODY; AMYLOID BETA PROTEIN; ANTIBODY; MUTANT PROTEIN; PEPTIDE; PROTEIN AGGREGATE; PROTEIN BINDING;

AMINO ACID SEQUENCE; ANTIBODY AFFINITY; ANTIBODY ENGINEERING; ANTIBODY SPECIFICITY; ANTIGEN BINDING; ARTICLE; BINDING SITE; CONFORMATION; DRUG DESIGN; ESCHERICHIA COLI; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN FOLDING; STOICHIOMETRY; CHEMISTRY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLUORESCENCE; HUMAN; IMMUNOLOGY; MOLECULAR GENETICS; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROCEDURES; PROTEIN ENGINEERING; PROTEIN SECONDARY STRUCTURE; WESTERN BLOTTING;

ALPHA-SYNUCLEIN; AMINO ACID SEQUENCE; AMYLOID BETA-PEPTIDES; ANTIBODIES; ANTIBODY SPECIFICITY; BLOTTING, WESTERN; ELECTROPHORESIS, POLYACRYLAMIDE GEL; ENZYME-LINKED IMMUNOSORBENT ASSAY; EPITOPES; FLUORESCENCE; HUMANS; INTRINSICALLY DISORDERED PROTEINS; ISLET AMYLOID POLYPEPTIDE; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; PEPTIDES; PROTEIN AGGREGATES; PROTEIN BINDING; PROTEIN ENGINEERING; PROTEIN STRUCTURE, SECONDARY; SINGLE-DOMAIN ANTIBODIES;

EID: 84938946548     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1422401112     Document Type: Article

References (53)

1. Carter PJ (2011) Introduction to current and future protein therapeutics: A protein engineering perspective. Exp Cell Res 317(9):1261-1269.
2. Elvin JG, Couston RG, van der Walle CF (2013) Therapeutic antibodies: Market considerations, disease targets and bioprocessing. Int J Pharm 440(1):83-98.
3. Goodman M (2009) Market watch: Sales of biologics to show robust growth through to 2013. Nat Rev Drug Discov 8(11):837-837.
4. Leader B, Baca QJ, Golan DE (2008) Protein therapeutics: A summary and pharmacological classification. Nat Rev Drug Discov 7(1):21-39.
5. Pavlou AK, Reichert JM (2004) Recombinant protein therapeutics: Success rates, market trends and values to 2010. Nat Biotechnol 22(12):1513-1519.
6. Bradbury AR, Sidhu S, Dübel S, McCafferty J (2011) Beyond natural antibodies: The power of in vitro display technologies. Nat Biotechnol 29(3):245-254.
7. Hoogenboom HR (2005) Selecting and screening recombinant antibody libraries. Nat Biotechnol 23(9):1105-1116.
8. Lee CC, Perchiacca JM, Tessier PM (2013) Toward aggregation-resistant antibodies by design. Trends Biotechnol 31(11):612-620.
9. Sidhu SS (2000) Phage display in pharmaceutical biotechnology. Curr Opin Biotechnol 11(6):610-616.
10. Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR (1994) Making antibodies by phage display technology. Annu Rev Immunol 12:433-455.
11. Miersch S, Sidhu SS (2012) Synthetic antibodies: Concepts, potential and practical considerations. Methods 57(4):486-498.
12. Babu MM, Kriwacki RW, Pappu RV (2012) Structural biology. Versatility from protein disorder. Science 337(6101):1460-1461.
13. Dunker AK, Brown CJ, Lawson JD, Iakoucheva LM, Obradović Z (2002) Intrinsic disorder and protein function. Biochemistry 41(21):6573-6582.
14. Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6(3):197-208.
15. Iakoucheva LM, Brown CJ, Lawson JD, Obradović Z, Dunker AK (2002) Intrinsic disorder in cell-signaling and cancer-associated proteins. J Mol Biol 323(3):573-584.
16. Tompa P (2012) Intrinsically disordered proteins: A 10-year recap. Trends Biochem Sci 37(12):509-516.
17. Uversky VN (2012) Intrinsically disordered proteins and novel strategies for drug discovery. Expert Opin Drug Discov 7(6):475-488.
18. Varadi M, et al. (2014) pE-DB: A database of structural ensembles of intrinsically disordered and of unfolded proteins. Nucleic Acids Res 42(Database issue): D326-D335.
19. Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN (2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J 272(20): 5129-5148.
20. Malaney P, Pathak RR, Xue B, Uversky VN, Davé V (2013) Intrinsic disorder in PTEN and its interactome confers structural plasticity and functional versatility. Sci Rep 3:2035.
21. Mészáros B, Simon I, Dosztányi Z (2011) The expanding view of protein-protein interactions: Complexes involving intrinsically disordered proteins. Phys Biol 8(3): 035003.
22. Uversky VN (2009) Intrinsic Disorder in Proteins Associated with Neurodegenerative Diseases. Protein Folding and Misfolding (Springer, New York), Vol 7, pp 21-75.
23. Uversky VN, Oldfield CJ, Dunker AK (2008) Intrinsically disordered proteins in human diseases: Introducing the D2 concept. Annu Rev Biophys 37:215-246.
24. Knowles TP, Vendruscolo M, Dobson CM (2014) The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol 15(6):384-396.
25. Schenk D, et al. (1999) Immunization with amyloid-β attenuates Alzheimer-diseaselike pathology in the PDAPP mouse. Nature 400(6740):173-177.
26. Näsström T, et al. (2011) Antibodies against alpha-synuclein reduce oligomerization in living cells. PLoS One 6(10):e27230.
27. Pantazes RJ, Maranas CD (2010) OptCDR: A general computational method for the design of antibody complementarity determining regions for targeted epitope binding. Protein Eng Des Sel 23(11):849-858.
28. Li T, Pantazes RJ, Maranas CD (2014) OptMAVEn: A new framework for the de novo design of antibody variable region models targeting specific antigen epitopes. PLoS One 9(8):e105954.
29. Yu C-M, et al. (2012) Rationalization and design of the complementarity determining region sequences in an antibody-antigen recognition interface. PLoS One 7(3): e33340.
30. Ladiwala ARA, et al. (2012) Rational design of potent domain antibody inhibitors of amyloid fibril assembly. Proc Natl Acad Sci USA 109(49):19965-19970.
31. Perchiacca JM, Ladiwala ARA, Bhattacharya M, Tessier PM (2012) Structure-based design of conformation- and sequence-specific antibodies against amyloid β. Proc Natl Acad Sci USA 109(1):84-89.
32. Perchiacca JM, Tessier PM (2012) Engineering aggregation-resistant antibodies. Annu Rev Chem Biomol Eng 3:263-286.
33. Kashmiri SV, De Pascalis R, Gonzales NR, Schlom J (2005) SDR grafting-a new approach to antibody humanization. Methods 36(1):25-34.
34. Ganesan A, et al. (2015) Selectivity of aggregation-determining interactions. J Mol Biol 427(2):236-247.
35. Zalevsky J, et al. (2010) Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157-159.
36. Sickmeier M, et al. (2007) Disprot: The database of disordered proteins. Nucleic Acids Res 35(Database issue):D786-D793.
37. Camilloni C, De Simone A, Vranken WF, Vendruscolo M (2012) Determination of secondary structure populations in disordered states of proteins using nuclear magnetic resonance chemical shifts. Biochemistry 51(11):2224-2231.
38. Sormanni P, Camilloni C, Fariselli P, Vendruscolo M (2015) The s2D method: Simultaneous sequence-based prediction of the statistical populations of ordered and disordered regions in proteins. J Mol Biol 427(4):982-996.
39. Barthelemy PA, et al. (2008) Comprehensive analysis of the factors contributing to the stability and solubility of autonomous human VH domains. J Biol Chem 283(6): 3639-3654.
40. Sormanni P, Aprile FA, Vendruscolo M (2015) The CamSol method of rational design of protein mutants with enhanced solubility. J Mol Biol 427(2):478-490.
41. Friguet B, Chaffotte AF, Djavadi-Ohaniance L, Goldberg ME (1985) Measurements of the true affinity constant in solution of antigen-antibody complexes by enzymelinked immunosorbent assay. J Immunol Methods 77(2):305-319.
42. Roodveldt C, et al. (2009) Chaperone proteostasis in Parkinson's disease: Stabilization of the Hsp70/α-synuclein complex by Hip. EMBO J 28(23):3758-3770.
43. Aprile FA, et al. (2013) Hsp70 oligomerization is mediated by an interaction between the interdomain linker and the substrate-binding domain. PLoS One 8(6):e67961.
44. Kabsch W, Sander C (1983) Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22(12): 2577-2637.
45. Camacho C, et al. (2009) BLAST+: Architecture and applications. BMC Bioinformatics 10:421.
46. Perchiacca JM, Ladiwala ARA, Bhattacharya M, Tessier PM (2012) Aggregationresistant domain antibodies engineered with charged mutations near the edges of the complementarity-determining regions. Protein Eng Des Sel 25(10):591-601.
47. Jespers L, Schon O, James LC, Veprintsev D, Winter G (2004) Crystal structure of HEL4, a soluble, refoldable human V(H) single domain with a germ-line scaffold. J Mol Biol 337(4):893-903.
48. Bond CJ, Marsters JC, Sidhu SS (2003) Contributions of CDR3 to V H H domain stability and the design of monobody scaffolds for naive antibody libraries. J Mol Biol 332(3): 643-655.
49. Laskowski RA, Rullmannn JA, MacArthur MW, Kaptein R, Thornton JM (1996) AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR. J Biomol NMR 8(4):477-486.
50. Gasteiger E, et al. (2005) The Proteomics Protocols Handbook (Springer, New York), pp 571-607.
51. Cremades N, et al. (2012) Direct observation of the interconversion of normal and toxic forms of α-synuclein. Cell 149(5):1048-1059.
52. Gasymov OK, Abduragimov AR, Glasgow BJ (2010) Excited protein states of human tear lipocalin for low- and high-affinity ligand binding revealed by functional AB loop motion. Biophys Chem 149(1-2):47-57.
53. Dunbar J, et al. (2014) SAbDab: The structural antibody database. Nucleic Acids Res 42(Database issue):D1140-D1146.