Probing the Specificity of Human Myeloma Proteins with a Random Peptide Phage Library

Abstract

Human myeloma proteins (HMPs) from 10 patients with multiple myeloma (MM) were used to affinity-select peptides from a random phage-display peptide library. Binding peptides were identified for the 10 analysed antibodies (eight, immunoglobulin G (IgG), and two, immunoglobulin A (IgA)). The specificity of the binding was confirmed by competitive experiments using phages and chemically synthesized peptides. Interestingly, some phage-displayed peptides were immuno-selected with HMPs isolated from different patients. Sequence alignments and homology searches revealed a significant homology with human proteins (e.g. neural cell adhesion proteins) and pathogen-derived proteins (e.g. herpes simplex virus capsid proteins). The selected peptides could be useful as targeting agents for myeloma cells expressing surface immunoglobulins.

Accurate identification of paraprotein antigen targets by epitope reconstruction

“…There have been several published attempts to identify antigens for multiple myeloma (MM) paraproteins by probing paraproteins with combinatorial peptide libraries. [1][2][3][4] The investigators tried to link the experimentally determined peptide epitopes with entries in the protein database. However, the published peptide sequences that were identified were insufficiently informative or accurate to yield meaningful database hits.…”

“…However, the published peptide sequences that were identified were insufficiently informative or accurate to yield meaningful database hits. [1][2][3][4] No predictions from the protein database search were experimentally validated.…”

Phage nanofibers in nanomedicine: Biopanning for early diagnosis, targeted therapy, and proteomics analysis

“…Cancer cell membrane receptors panning Extracellular matrix integrin α v β 3 RGD (Healy et al, 1995) α v β 3 / β 5 integrin CDCRGDCFC (Koivunen, Wang, & Ruoslahti, 1995) β 2 integrin CPCFLLGCC (Koivunen et al, 2001) Fibroblast growth factor (FGF)8b HSQAAVP (Wang et al, 2013) FGF PLLQATL (Wu et al, 2010) aFGF AGNWTPI (Dai et al, 2014) Fibroblast growth factor receptor (FGFR) FPSMYV (Fan et al, 2002) Programmed death-ligand 1 (PD-L1) GSGSGSTYLCG AISLAPKAQIKESL (Caldwell et al, 2017) Vascular endothelial growth factor (VEGF) ATWLPPR, WHLPFKC, (Binétruy- Tournaire et al, 2000;Erdag et al, 2007) Vascular endothelial growth factor receptor (VEGFR)-3 CSDSWHYWC (Qin et al, 2007) VEGFR YHWYGYTPQNVI (Li et al, 2005) VEGFR Flt-1 WHSDMEWWYLLG (An et al, 2004) Aminopeptidase A CPRECESIC (Marchiò et al, 2004) Aminopeptidase P CPGPEGAGC (Essler & Ruoslahti, 2002) Aminopeptidase N CNGRC (Pasqualini et al, 2000) Cluster Human myeloma protein FHEPENSISVNQLDC (Dybwad, Lambin, Sioud, & Zouali, 2003) Neuron-glial antigen (NG)2 proteoglycan TAASGVRSM, LTLRWVGLMS (Burg, Pasqualini, Arap, Ruoslahti, & Stallcup, 1999) Myeloma-proteins YIHYIF (Szecsi et al, 1999) Matrix Metalloproteinase-2 (MMP2) HWWQWPSSLQLRGGGS, HNWTRWLLHPDRGGGS (Lu et al, 2012) Matrix Metalloproteinase-2-processed collagen IV TLTYTWS (Mueller, Gaertner, Blechert, Janssen, & Essler, 2009) Interleukin-6 receptor (gp80) LSLITRL (Su et al, 2005) Interleukin-receptor (IL-4) CRKRLDRNC (Continues)…”

Caracterização de um peptídeo selecionado por Phage Display com atividade anti-tumoral

“…No caso das bibliotecas de peptídeos, elas compreendem um número grande de peptídeos, entre 10 7 -10 9 , onde suas sequências são geradas de maneira aleatória a partir de resíduos diversos de aminoácidos. Em forma linear ou circular, esses peptídeos expressos, possuem a capacidade de mimetizar tanto estruturas conformacionais, quanto epítopos (contínuos ou descontínuos; ROMANOV et al, 2001;DYBWAD et al, 2003;ZAMBRANO-MILA et al, 2020). Na área de pesquisa sobre o câncer, o emprego desses peptídeos é interessante, pois possuem baixa toxicidade e alta especificidade em testes diagnósticos e terapêuticos, além da possibilidade da combinação com outras terapias convencionais para o tratamento do câncer, ajudando na redução de seus efeitos colaterais.…”