The BDB database (http://immunet.cn/bdb) is an update of the MimoDB database, which was previously described in the 2012 Nucleic Acids Research Database issue. The rebranded name BDB is short for Biopanning Data Bank, which aims to be a portal for biopanning results of the combinatorial peptide library. Last updated in July 2015, BDB contains 2904 sets of biopanning data collected from 1322 peer-reviewed papers. It contains 25 786 peptide sequences, 1704 targets, 492 known templates, 447 peptide libraries and 310 crystal structures of target-template or target-peptide complexes. All data stored in BDB were revisited, and information on peptide affinity, measurement method and procedures was added for 2298 peptides from 411 sets of biopanning data from 246 published papers. In addition, a more professional and user-friendly web interface was implemented, a more detailed help system was designed, and a new on-the-fly data visualization tool and a series of tools for data analysis were integrated. With these new data and tools made available, we expect that the BDB database would become a major resource for scholars using phage display, with improved utility for biopanning and related scientific communities.

Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4.5 hours to yield a “naïve” library), and libraries chemically modified by aldehyde ligation and cysteine macrocyclization {M} characterized by paired-end deep sequencing, detected a significant drop in diversity in {L} → {N}, but only a minor compositional difference in {S} → {L} and {N} → {M}. Libraries expressed at the N-terminus of phage protein pIII censored positively charged amino acids Arg and Lys; libraries expressed between pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde ligation and cysteine macrocyclization unveiled censorship of sequences with Ser/Phe. Analogous analysis can be used to explore library diversity in new display platforms and optimize cPTM of these libraries.

Polystyrene surface-binding peptides (PSBPs) are useful as affinity tags to build a highly effective ELISA system. However, they are also a quite common type of target-unrelated peptides (TUPs) in the panning of phage-displayed random peptide library. As TUP, PSBP will mislead the analysis of panning results if not identified. Therefore, it is necessary to find a way to quickly and easily foretell if a peptide is likely to be a PSBP or not. In this paper, we describe PSBinder, a predictor based on SVM. To our knowledge, it is the first web server for predicting PSBP. The SVM model was built with the feature of optimized dipeptide composition and 87.02% (MCC = 0.74; AUC = 0.91) of peptides were correctly classified by fivefold cross-validation. PSBinder can be used to exclude highly possible PSBP from biopanning results or to find novel candidates for polystyrene affinity tags. Either way, it is valuable for biotechnology community.

SAROTUP (Scanner And Reporter Of Target-Unrelated Peptides) 3.1 is a significant upgrade to the widely used SAROTUP web server for the rapid identification of target-unrelated peptides (TUPs) in phage display data. At present, SAROTUP has gathered a suite of tools for finding potential TUPs and other purposes. Besides the TUPScan, the motif-based tool, and three tools based on the BDB database, i.e., MimoScan, MimoSearch, and MimoBlast, three predictors based on support vector machine, i.e., PhD7Faster, SABinder and PSBinder, are integrated into SAROTUP. The current version of SAROTUP contains 27 TUP motifs and 823 TUP sequences. We also developed the standalone SAROTUP application with graphical user interface (GUI) and command line versions for processing deep sequencing phage display data and distributed it as an open source package, which can perform perfectly locally on almost all systems that support C++ with little or no modification. The web interfaces of SAROTUP have also been redesigned to be more self-evident and user-friendly. The latest version of SAROTUP is freely available at http://i.uestc.edu.cn/sarotup3 .

Vascular endothelial growth factor (VEGF), one of the most important angiogenic factors, plays an essential role in both physiological and pathological angiogenesis through binding to VEGF receptors (VEGFRs). Here we report a novel peptide designated HRHTKQRHTALH (peptide HRH), which was isolated from the Ph.D. -12 phage display library using VEGFR-Fc fusion protein as the bait. This peptide was found to dose-dependently inhibit the proliferation of human umbilical vein endothelial cells stimulated by VEGF. The anti-angiogenesis effect of the HRH peptide was further confirmed in vivo using the chick chorioallantoic membrane assay, which was also dose-dependent. Besides, peptide HRH was proved to inhibit corneal neovascularization in an alkali-burnt rat corneal model and a suture-induced rat corneal model. Taken together, these findings suggest that the HRH peptide can inhibit angiogenesis both in vitro and in vivo. Consequently, the HRHTKQRHTALH peptide might be a promising lead peptide for the development of potential angiogenic inhibitors.