Selection and characterization of Anticalins targeting human prostate-specific membrane antigen (PSMA)

Protein Engineering, Design & Selection : PEDS
Cyril BarinkaA Skerra

Abstract

Although prostate carcinoma (PCa) is by far the most commonly diagnosed neoplasia in men, corresponding diagnostic and therapeutic modalities have limited efficacy at present. Anticalins comprise a novel class of binding proteins based on a non-immunoglobulin scaffold that can be engineered to specifically address molecular targets of interest. Here we report the selection and characterization of Anticalins that recognize human prostate-specific membrane antigen (PSMA), a membrane-tethered metallopeptidase constituting a disease-related target for imaging and therapy of PCa as well as solid malignancies in general. We used a randomized lipocalin library based on the human lipocalin 2 (Lcn2) scaffold together with phage display and ELISA screening to select PSMA-specific variants. Five Anticalin candidates from the original panning were expressed in Escherichia coli as soluble monomeric proteins, revealing affinities toward PSMA down to the low nanomolar range. Binding characteristics of the most promising candidate were further improved via affinity maturation by applying error-prone PCR followed by selection via phage display as well as bacterial surface display under more stringent conditions. In BIAcore measurements, the dis...Continue Reading

References

Nov 11, 1999·Journal of Molecular Recognition : JMR·D G Myszka
May 21, 2004·Protein Science : a Publication of the Protein Society·Cyril BarinkaJan Konvalinka
May 30, 2006·Clinical Genitourinary Cancer·Kevin A DavidNeil H Bander
May 22, 2008·Journal of Molecular Recognition : JMR·Gregory De CrescenzoBala Srinivasan
Feb 21, 2009·Journal of the American Chemical Society·Hyun Jin KimArne Skerra
Jul 5, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Mary K SamplaskiDonna E Hansel
Jan 11, 2012·Methods in Enzymology·Michaela Gebauer, Arne Skerra
Feb 7, 2012·Current Medicinal Chemistry·C A FossM G Pomper
Feb 7, 2012·Current Medicinal Chemistry·D V FerrarisT Tsukamoto
Aug 23, 2012·The Prostate·Jessie R Nedrow-ByersClifford E Berkman
Jan 11, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·John A BarrettJohn W Babich
Apr 18, 2013·Current Topics in Medicinal Chemistry·Ronnie C MeaseMartin G Pomper
Nov 21, 2014·European Journal of Nuclear Medicine and Molecular Imaging·Ali Afshar-OromiehUwe Haberkorn

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Citations

May 12, 2018·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Christine Rothe, Arne Skerra
Jun 12, 2020·Nucleic Acids Research·Jakub PtacekCyril Barinka
May 29, 2020·Protein Science : a Publication of the Protein Society·Friedrich-Christian DeuschleArne Skerra
Sep 1, 2018·Protein Science : a Publication of the Protein Society·Jakub PtacekCyril Barinka
Sep 17, 2020·International Journal of Molecular Sciences·Zora NovakovaCyril Barinka
Jul 29, 2017·Biophysics Reviews·R BedfordDarren C Tomlinson
Jan 29, 2021·Journal of Virology·Veronika KrchlíkováDaniel Elleder
Sep 28, 2017·Journal of Medicinal Chemistry·Petra DvořákováJan Konvalinka

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