Interactions between molecules are ubiquitous and occur in our bodies, the food we eat, the air we breathe, and myriad additional contexts. Although numerous tools are available for the recognition of biomolecular interactions, such tools are often limited in their sensitivity, expensive, and difficult to modify for various uses. In contrast, the quartz crystal microbalance (QCM) has sub-nanogram detection capabilities, is label-free, is inexpensive to create, and can be readily modified with a number of diverse surface chemistries to detect and characterize diverse interactions. To maximize the versatility of the QCM, scientists need to know available methods by which QCM surfaces can be modified. Therefore, in addition to summarizing the various tools currently used for biomolecular recognition, explicating the fundamental principles of the QCM as a tool for biomolecular recognition, and comparing the QCM with other acoustic sensors, we systematically review the numerous types of surface chemistries-including hydrophobic bonds, ionic bonds, hydrogen bonds, self-assembled monolayers, plasma-polymerized films, photochemistry, and sensing ionic liquids-used to functionalize QCMs for various purposes. We also review the QCM's diverse applications, which include the detection of gaseous species, detection of carbohydrates, detection of nucleic acids, detection of non-enzymatic proteins, characterization of enzymatic activity, detection of antigens and antibodies, detection of cells, and detection of drugs. Finally, we discuss the ultimate goals of and potential barriers to the development of future QCMs.

alpha(1)-Antitrypsin (AT) is a major proteinase inhibitor within the lung. The Z variant of AT (E342K) polymerizes within the liver and lung, resulting in hepatic aggregation of AT and tissue deficiency, predisposing to early onset of cirrhosis and emphysema, respectively. Polymerization of the aberrant protein can be prevented in vitro by specific peptides such as FLEAIG. This peptide serves as a lead molecule to design a shorter peptide that may be effective as a therapeutic agent. In this study we employed a systematic chemical approach using alanine scanning of Ac-FLEAIG-OH and subsequent peptide shortening to study the binding of shorter peptides to Z-AT. While two additional 6-mer peptides Ac-FLAAIG-OH and Ac-FLEAAG-OH were found to bind to Z-AT, their daughter peptides Ac-FLEAA-NH(2) and Ac-FLAA-NH(2) also bound avidly to Z-AT and prevented polymerization of the protein. Further comparative studies revealed that the binding of Ac-FLAA-NH(2) was more specific for Z-AT. The peptide-AT complex formation was enhanced by the presence of C-terminal amide group on the peptide, and circular dichroism analysis demonstrated that a random coil rather than a beta-helical conformation favored binding of the peptide to AT. In summary, this study has identified novel small peptides that inhibit Z-AT polymerization, and are a significant advance towards the treatment of Z-AT-related cirrhosis and emphysema.

IntroductionThe ␣1-antitrypsin (AT) is the most abundant circulating protease inhibitor in plasma (1-2 mg/ml) and a prototypical member of the serpin (serine protease inhibitor) superfamily [1,2]. It is primarily synthesized by the hepatocyte and enters the lung by passive diffusion to protect the alveolar matrix from proteolysis, particularly by neutrophil elastase [1][2][3][4][5][6]. The secondary structure of active AT is composed of three ␤-sheets (A, B and C), nine ␣-helices (A-I), and a reactive centre loop (RCL) which tightly entraps neutrophil elastase and other target proteases [6][7][8] [10][11][12]. The accumulation of Z-AT polymers within the hepatocyte causes liver cirrhosis and the resultant plasma deficiency can give rise to early-onset emphysema [13][14][15][16][17]. Polymerization of other serpin variants such as those of antithrombin III, ␣1-antichymotrypsin, C1-inhibitor and neuroserpin have also been described and related to thrombosis, emphysema, angioedema and dementia, respectively [18, 19]. [18,[20][21][22][23][24] Given that protein aggregation is the origin for the pathogenesis of the liver and lung diseases associated with Z-AT, the crux of the matter is to inhibit the oligomerization process and thus prevent the intracellular accumulation of Z-AT polymers. Previous studies have shown that 11-to 13-mer synthetic peptides with homology to the RCL could anneal to the A-sheet of AT

Two types of new alginate-based wound dressings, Type-AP and Type-AE, were fabricated by the EDC-activated crosslinking of alginate with Polyethyleneimine and Ethylenediamine, respectively. As compared with the commercial non-woven wound dressing, Kaltostat, both Type-AP and Type-AE dressings had higher degradation temperature, lower calcium content, and a sponge-like macroporous structure. In addition, these two alginate-based dressings had higher mechanical stress (12.37 +/- 1.72 and 6.87 +/- 0.5 MPa for Type-AP and -AE, respectively) and higher water vapor transmission rates (both about 3,500 g/m2/day) than Kaltostat (0.87 +/- 0.12 MPa and 2,538 g/m2/day). Fibroblasts proliferated faster on these two newly developed wound dressings at a higher rate as compared with that on Kalostat dressing. The results of animal study showed that the wounds treated with either Type-AP or Type-AE dressings healed faster than Kaltostat with less encapsulation of residuals by fibrous tissue and more neo-capillary formation. These two newly developed Type-AP and Type-AE porous wound dressings thus have great potential for clinical applications.

α-Conotoxins are peptide neurotoxins that selectively inhibit various subtypes of nicotinic acetylcholine receptors. They are important research tools for studying numerous pharmacological disorders, with profound potential for developing drug leads for treating pain, tobacco addiction, and other conditions. They are characterized by the presence of two disulfide bonds connected in a globular arrangement, which stabilizes a bioactive helical conformation. Despite extensive structure-activity relationship studies that have produced α-conotoxin analogs with increased potency and selectivity towards specific nicotinic acetylcholine receptor subtypes, the efficient production of diversity-oriented α-conotoxin combinatorial libraries has been limited by inefficient folding and purification procedures. We have investigated the optimized conditions for the reliable folding of α-conotoxins using simplified oxidation procedures for use in the accelerated production of synthetic combinatorial libraries of α-conotoxins. To this end, the effect of co-solvent, redox reagents, pH, and temperature on the proportion of disulfide bond isomers was determined for α-conotoxins exhibiting commonly known Cys loop spacing frameworks. In addition, we have developed high-throughput 'semi-purification' methods for the quick and efficient parallel preparation of α-conotoxin libraries for use in accelerated structure-activity relationship studies. Our simplified procedures represent an effective strategy for the preparation of large arrays of correctly folded α-conotoxin analogs and permit the rapid identification of active hits directly from high-throughput pharmacological screening assays.

The α4β2 nicotinic acetylcholine receptor (nAChR) is an important target for currently approved smoking cessation therapeutics. However, the development of highly selective α4β2 nAChR antagonists remains a significant challenge. α-Conotoxin GID is an antagonist of α4β2 nAChRs, though it is significantly more potent toward the α3β2 and α7 subtypes. With the goal of obtaining further insights into α-conotoxin GID/nAChR interactions that could lead to the design of GID analogues with improved affinity for α4β2 nAChRs, we built a homology model of the GID/α4β2 complex using an X-ray co-crystal structure of an α-conotoxin/acetylcholine binding protein (AChBP) complex. Several additional interactions that could potentially enhance the affinity of GID for α4β2 nAChRs were observed in our model, which led to the design and synthesis of 22 GID analogues. Seven analogues displayed inhibitory activity toward α4β2 nAChRs that was comparable to GID. Significantly, both GID[A10S] and GID[V13I] demonstrated moderately improved selectivity toward α4β2 over α3β2 when compared with GID, while GID[V18N] exhibited no measurable inhibitory activity for the α3β2 subtype, yet retained inhibitory activity for α4β2. In this regard, GID[V18N] is the most α4β2 nAChR selective α-conotoxin analogue identified to date.

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Gas sensing technologies are of importance for a variety of industrial, environmental, medical, and even military applications. Many gases, such as man-made or naturally occurring volatile organic compounds (VOCs), can adversely affect human health or cause harm to the environment. Recent advances in “designer solvents” and sensor technologies have facilitated the development of ultrasensitive gas sensing ionic liquids (SILs) based on quartz crystal microbalance (QCM) that can real-time detect and discriminate VOCs. Based on specific chemical reactions at room temperature, thin-coated functionalized ionic liquids on quartz chips are able to capture VOCs chemoselectively with a single-digit parts-per-billion detection limit. The amalgamation of tailor-made functional SILs and QCM results in a new class of qualitative and semiquantitative gas sensing device, which represents a prototype of electronic nose. This review vignettes some conventional gas sensing approaches and collates latest research results in the exploration of SIL-on-QCM chips and gives an account of the state-of-the-art gas sensing technology.