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• ComProM -QSRR methodology has been developed for the prediction of retention time of peptides in liquid chromatography. • It identifies physicochemical properties at specific positions in the peptide sequences that modulate the retention time. • The prediction works well for all classes of peptides irrespective of size or sequence. • It is simple and straightforward approach to execute for retention time prediction. Peptide therapeutics plays a prominent role in medical practice. Both peptides and proteins have been used in several disease conditions like diabetes, cancer, bacterial infections etc. The optimization of a peptide library is a time consuming and expensive chore. The tools of computational chemistry offer a way to optimize the properties of peptides. Quantitative Structure Retention (Chromatographic) Relationships (QSRR) is a powerful tool which statistically derives relationships between chromatographic parameters and descriptors that characterize the molecular structure of analytes. In this paper, we show how Com parative Pro tein M odeling Q uantitative S tructure R etention R elationship (acronym ComProM -QSRR) can be used to predict the retention time of peptide sequences. This formalism is founded on our earlier published QSAR methodology Homo SAR. ComProM -QSRR can recognize and distinguish the contribution of amino acids at specific positions in the peptide sequences to the retention phenomena through their related physicochemical properties. This study firmly establishes the fact that this approach can be pragmatically used to predict the retention time to all classes of peptides regardless of size or sequence. [ABSTRACT FROM AUTHOR]

• Development of an efficient clean-up strategy for short peptides in plasma. • Comparison of 4 different clean-up protocols (advantages and disadvantages). • Untargeted peptidomic approach for short peptide identification in plasma. • Identification of 91 short peptides, the largest number never identified before. • Development of a rapid and simple method for clinical applications. Short peptides, namely di- tri- and tetra peptides, have been proven to play an important diagnostic role in several diseases. Therefore, the development of an analytical approach for their detection and identification is nowadays an important research goal. This paper describes an analytical procedure able to overcome the issues of short peptide isolation, clean-up and identification in plasma samples. Four different protocols were compared and tested to maximize both recovery and total number of identifications of short circulating plasma endogenous peptides. The purified peptides, coming from the four different tested protocols, were separated by zwitterionic hydrophilic liquid chromatography coupled to high-resolution mass spectrometry with the purpose of accomplishing an untargeted investigation based on suspect screening for short peptides in plasma. In particular, the use of Phree™ Phospholipid removal cartridge in combination with a purification step by solid phase extraction on a graphitized carbon black sorbent allowed the identification of the largest number of amino acid sequences (91 short peptides). The clean-up procedure allowed to tackle the issue of the low abundance of such peptides and their suppression during mass-spectrometric analysis. The results indicated that sample preparation is therefore fundamental for short peptide analysis in plasma samples. [ABSTRACT FROM AUTHOR]