X-Pro peptides: synthesis and solution conformation of benzyloxycarbonyl-(Aib-Pro)<SUB>4</SUB>methyl ester. Evidence for a novel helical structure

The synthesis of the octapeptide, benzyloxycarbonyl-(&#945;-aminoisobutyryl-L-prolyl)4-methyl ester [Z-(Aib-Pro)4-OMe] and an analysis of its solution conformation is reported. The octapeptide is shown to possess three strong intramolecular hydrogen bonds on the basis of studies of the solvent and temperature dependence of NH chemical shifts and rates of hydrogen-deuterium exchange. 13C studies are consistent with a structure involving only trans Aib-Pro bonds, while ir experiments support a hydrogen-bonded conformation. The Aib 3, 5, and 7 NH groups are shown to participate in hydrogen bonding. A 310 helical conformation compatible with the spectroscopic data is suggested. The proposed conformation consists of three type III &#946;-turns with Aib and Pro at the corners and stabilized by 4&#8594; 1 intramolecular hydrogen bonds

Comparative Analysis of Classification Models on Income Prediction

Predictive Analytics is the underlying technology that can simply be described as an approach to scientifically utilize the past to predict the future to help coveted results. It is the branch of cutting edge analytics which is utilized to make predictions about unfamiliar events. Predictive analytics utilizes different procedures from information mining, insights, modeling, machine learning and artificial Intelligence. It includes extraction of data from information and is utilized to predict patterns and behavior patterns. It can be connected to an unfamiliar event or interest whether past, present or future. It helps being used of statistical algorithms information and machine learning strategies to distinguish the probability of future results in light of chronicled information. Income Determination is an important application of predictive analytics where customer segmentation takes place based on different demographical data. In this paper, we attempt to identify this purpose with a novel approach using different classification techniques to minimize the risk and cost involved to predict certain income levels. Here we have demonstrated the performance of each algorithm particularly on identification of customers using classification techniques. In addition, we provide an investigation analysis on true positives, false negatives, scored labels and scored probabilities

Remote surface inspection system

This paper reports on an on-going research and development effort in remote surface inspection of space platforms such as the Space Station Freedom (SSF). It describes the space environment and identifies the types of damage for which to search. This paper provides an overview of the Remote Surface Inspection System that was developed to conduct proof-of-concept demonstrations and to perform experiments in a laboratory environment. Specifically, the paper describes three technology areas: (1) manipulator control for sensor placement; (2) automated non-contact inspection to detect and classify flaws; and (3) an operator interface to command the system interactively and receive raw or processed sensor data. Initial findings for the automated and human visual inspection tests are reported

Gramicidin S: A peptide model for protein glycation and reversal of glycation using nucleophilic amines

Nonenzymatic glycation of proteins has been implicated in various diabetic complications and age-related disorders. Proteins undergo glycation at the N-terminus or at the ε-amino group of lysine residues. Glycation of proteins proceeds through the stages of Schiff base formation, conversion to ketoamine product and advanced glycation end products. Gramicidin S, which has two ornithine residues, was used as a model system to study the various stages of glycation of proteins using electrospray ionization mass spectrometry. The proximity of two ornithine residues in the peptide favors the glycation reaction. Formation of advanced glycation end products and diglycation on ornithine residues in gramicidin S were observed. The formation of Schiff base adduct is reversible, whereas the Amadori rearrangement to the ketoamine product is irreversible. Nucleophilic amines and hydrazines can deglycate the Schiff base adduct of glucose with peptides and proteins. Hydroxylamine, isonicotinic acid hydrazide and aminoguanidine effectively removed glucose from the Schiff base adduct of gramicidin S. Hydroxylamine is more effective in deglycating the adduct compared with isonicotinic acid hydrazide and aminoguanidine. The observation that the hydrazines are effective in deglycating the Schiff base adduct even in the presence of high concentrations of glucose, may have a possible therapeutic application in preventing complications of diabetes mellitus. Hydrazines may be used to distinguish between the Schiff base and the ketoamine products formed at the initial stages of glycation

Stereochemistry of Schellman motifs in peptides: crystal structure of a hexapeptide with a C-terminus 6 →1 hydrogen bond

The Schellman motif is a widely observed helix terminating structural motif in proteins, which is generated when the C-terminus residue adopts a left-handed helical (&#945;L) conformation. The resulting hydrogen-bonding pattern involves the formation of an intramolecular 6&#8594;1 interaction. This helix terminating motif is readily mimicked in synthetic helical peptides by placing an achiral residue at the penultimate position of the sequence. Thus far, the Schellman motif has been characterized crystallographically only in peptide helices of length 7 residues or greater. The structure of the hexapeptide Boc-Pro-Aib-Gly-Leu-Aib-Leu-OMe in crystals reveal a short helical stretch terminated by a Schellman motif, with the formation of 6 &#8594; 1 C-terminus hydrogen bond. The crystals are in the space group P212121 with a = 18.155(3) &#197;, b = 18.864(8) &#197;, c = 11.834(4) &#197;, and Z = 4 . The final R1 and wR2 values are 7.68 and 14.6%, respectively , for 1524 observed reflections [Fo &#8805; 3&#962;(Fo)]. A 6 &#8594;1 hydrogen bond between Pro(1)CO &#183; &#183; &#183; Leu(6)NH and a 5 &#8594;2 hydrogen bond between Aib(2)CO &#183; &#183; &#183; Aib(5)NH are observed. An analysis of the available oligopeptides having an achiral Aib residue at the penultimate position suggests that chain length and sequence effects may be the other determining factors in formation of Schellman motifs

Spermidine as a potential biosynthetic precursor to the 1,5-diazabicyclo[4:3:0]nonene residue in the efrapeptins

Efrapeptins (1±3

The crystal structure of benzyloxycarbonyl-(α-aminoisobutyryl)-L-alanyl methyl ester

Crystals of the title compound, C20,H29,N3,O6, are monoclinic, space group P2, with a = 8-839 (3), b = f10.818 (3), c = 11.414 (2) A, &#946; = 95.69 (2)&#176; Z = 2; final R = 0.053. The molecular conformation is defined by the following angles (&#966;, &#968;): Aib-1 58- 1, 36.8; Aib-2 68.3, 18.6; Ala-3 (&#966;) -136.2&#176;. The molecule adopts a type 111 &#946; -turn conformation stabilized by an intramolecular hydrogen bond between the CO of the benzyloxycarbonyl group and the NH of the alanyl residue. The hydrogen-bond parameters are N&#183;&#183;&#183;O 2-904 &#197; and &#8736;NH&#183;&#183;&#183;O 156.9&#176;

Thermal stabilization of thymidylate synthase by engineering two disulfide bridges across the dimer interface

Thermal inactivation of oligomeric enzymes is most often irreversible and is frequently accompanied by precipitation. We have engineered two symmetry related disulfide bridges (155-188′ and 188-155′) across the subunit interface of Lactobacillus casei thymidylate synthase, at sites chosen on the basis of an algorithm for the introduction of stereochemically unstrained bridges into proteins. In this communication, we demonstrate a remarkable enhancement in the thermal stability of the covalently cross-linked double disulfide containing dimeric enzyme. The mutant enzyme remains soluble and retains secondary structure even at 90°C, in contrast to the wild-type enzyme which precipitates at 52°C. Furthermore, the mutant enzyme has a temperature optimum of 55°C and possesses appreciable enzymatic activity at 65°C. Cooling restores complete activity, in the mutant protein, demonstrating reversible thermal unfolding. The results suggest that inter-subunit crosslinks can impart appreciable thermal stability in multimeric enzymes

Effect of amino acid substitutions at the subunit interface on the stability and aggregation properties of a dimeric protein: role of Arg 178 and Arg 218 at the dimer interface of thymidylate synthase

The significance of two interface arginine residues on the structural integrity of an obligatory dimeric enzyme thymidylate synthase (TS) from Lactobacillus casei was investigated by thermal and chemical denaturation. While the R178F mutant showed apparent stability to thermal denaturation by its decreased tendency to aggregate, the Tm of the R218K mutant was lowered by 5°C. Equilibrium denaturation studies in guanidinium chloride (GdmCl) and urea indicate that in both the mutants, replacement of Arg residues results in more labile quaternary and tertiary interactions. Circular dichroism studies in aqueous buffer suggest that the protein interior in R218K may be less well-packed as compared to the wild type protein. The results emphasize that quaternary interactions may influence the stability of the tertiary fold of TS. The amino acid replacements also lead to notable alteration in the ability of the unfolding intermediate of TS to aggregate. The aggregated state of partially unfolded intermediate in the R178F mutant is stable over a narrower range of denaturant concentrations. In contrast, there is an exaggerated tendency on the part of R218K to aggregate in intermediate concentrations of the denaturant. The 3 Å crystal structure of the R178F mutant reveals no major structural change as a consequence of amino acid substitution. The results may be rationalized in terms of mutational effects on both the folded and unfolded state of the protein. Site specific amino acid substitutions are useful in identifying specific regions of TS involved in association of non-native protein structures