Eight cyclic analogs and corresponding linear homologs of the alpha-factor mating pheromone (WHWLQLKPGQPMY) of Saccharomyces cerevisiae were synthesized using solid-phase procedures on a phenylacetamidomethyl support. On-resin lactamization of the side chains of residues 7 and 10 to form rings containing from 14 to 18 atoms was effected by the BOP reagent. All peptides were highly homogeneous and gave expected molecular ions by FAB mass spectrometry. The constrained analogs had biological activities varying from 10% to less than 0.1% of that of [Nle12]-alpha-factor. In all cases, cyclic analogs with Glu in position 10 were more active than the homolog with Asp at this position. This trend was also found with the corresponding linear pheromones, suggesting that a gamma-carbonyl in position 10 is an important determinant of pheromone potency. The cyclic peptides had from 50- to 20000-fold lower affinities for the alpha-factor receptor than for [Nle12]-alpha-factor, as judged using a competition binding assay. Circular dichroism studies indicate that the cyclic lactam-containing region of cyclo7.10[Orn7, Glu10,Nle12]-alpha-factor retains a beta-turn-like structure similar to that found in the corresponding model tetrapeptide. The results show that covalently constrained analogs of the linear pheromone can maintain biological activity, despite binding poorly to the receptor, and indicate that a beta-turn-like structure in the center of the pheromone allows signal transduction.

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Flaky tests have gained attention from the research community in recent years and with good reason. These tests lead to wasted time and resources, and they reduce the reliability of the test suites and build systems they affect. However, most of the existing work on flaky tests focus exclusively on traditional unit tests. This work ignores UI tests that have larger input spaces and more diverse running conditions than traditional unit tests. In addition, UI tests tend to be more complex and resourceheavy, making them unsuited for detection techniques involving rerunning test suites multiple times. In this paper, we perform a study on flaky UI tests. We analyze 235 flaky UI test samples found in 62 projects from both web and Android environments. We identify the common underlying root causes of flakiness in the UI tests, the strategies used to manifest the flaky behavior, and the fixing strategies used to remedy flaky UI tests. The findings made in this work can provide a foundation for the development of detection and prevention techniques for flakiness arising in UI tests.

Analogues of the α‐factor mating pheromone (WHWLQLKPGQPMY) from Saccharomyces cerevisiae in which the side chains of residues 7 and 10 were joined by lactam bonds were studied by nmr and molecular modeling. These investigations were carried out to discern the effect of lactam ring size on conformation and to ascertain whether the side chain i to i + 3 cyclized tetramers [H. R. Marepalli et al. (1996) Journal of the American Chemical Society, Vol. 118, pp. 6531–6539] can be considered as conformation‐constraining building blocks when introduced into a long peptide chain. Nuclear Overhauser effect constraints, temperature coefficients, and backbone torsional angles were derived from 1H‐nmr spectra measured in DMSO‐d6. Modeling studies using the above constraints indicate that the lactam regions of the tridecapeptides assume various combinations of type II β‐turns, γ‐turns, and γ′‐turns, but never type I β‐turns. These investigations provide evidence that the tetrapeptide building blocks retain their preferred conformations in larger molecules and can be used to control the architecture of regions of such peptides. © 1998 John Wiley & Sons, Inc. Biopoly 45: 21–34, 1998