Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins

Abstract

The most abundant proteins in serum, such as albumin and IgG, act as molecular sponges that bind and transport low molecular weight proteins/peptides and drugs. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. Advances in these fields will open new avenues of tailor-made molecular therapy, reducing present limitations on treatment arising from toxicity and inefficiency. In this short review we report and discuss the most recent developments arising from the use of proteomic tools in blood plasma protein research, looking at the identification of proteins found in plasma as well as their interactions with small molecules such as drugs, peptides, organic chemicals and metals. We believe this research demonstrates that proteomic technologies, and in particular pharmacoproteomics, interactomics and post-translational modification analysis, could be instrumental in the design of new tailor-made drugs leading to substantial improvements in molecular therapy.

In Silico Analyses of Proteomic Data Suggest a Role for Heat Shock Proteins in Umbilical Cord Blood Hematopoietic Stem Cells

“…This kind of approach is known as interactomics. Interactomics is a fusion science of biology, informatics and engineering which provides a global view of protein family interaction networks [36]. It involves the study of both the interactions and the consequences of those interactions between and among proteins, and other molecules within a cell and can be used to compare networks of interaction between and within species to see how the traits of such networks are varied and conserved.…”

Thermodynamic profile of the plasma proteome for malignancies

“…Това би могло да се свърже с факта, че миеломът при леките вериги е по-агресивен от типичната ММ форма (Dispenzieri et al, 2009;Siegel et al, 2009). Отместването на прехода на HSА вероятно е свързано със способността му да се свързва с многобройни серумни белтъци и/или лиганди (Ascenzi and Fasano, 2010;Fasano et al, 2005;Varshney et al, 2010;Zolla, 2008;). Стабилизиране на албумина се наблюдава например при свързването му с октаноат, каприлат, N-Ac-L-триптофан и други хидрофобни мастни киселини (Ankaru et al, 2004;Shrake and Ross, 1988), както и с лиганда бромокрезол (Фигура 14, Garbett et al, 2009).…”

“…Така, установяването на различни групи от ДСК термограми от серум на ММ пациенти очевидно е свързано с многообразието на модификациите в серумния протеом, което се дължи на мрежа от взаимодействия, включваща белтък-белтък и белтък-лиганд взаимодействия ("интерактомика") (Zolla, 2008;Zhou et al, 2004). Тази хетерогенност на ММ термограмите не е изненадваща и е в пълно в съгласие с определението на множествения миелом като, не една болест, а по-скоро много", като всеки един от подтиповете ММ са дефинирани от множество специфични генни и цитогенни нарушения (Fonseca et al, 2009;Moreaux et al, 2011).…”

The Proteomics Big Challenge for Biomarkers and New Drug-Targets Discovery

“…In addition to the above listed technical limitations, it is also important to consider the patients/controls individual variability. Since a variety of factors may influence each individual profile, we cannot assume that drug responses will be similar in healthy or diseased group [114]. Another important factor which cannot be underestimated is the time between drug treatment/administration and analysis.…”