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Single-conformation IR and UV spectroscopy of the prototypical capped γ-peptide Ac-γ4-Phe-NHMe (γ4F) was carried out under jet-cooled conditions in the gas phase in order to understand its innate conformational preferences in the absence of a solvent. We obtained conformer-specific IR and UV spectra and compared the results with calculations to make assignments and explore the differences between the γ2- and γ4-substituted molecules. We found four conformers of γ4F in our experiment. Three conformers form nine-membered hydrogen-bonded rings (C9) enclosed by an NH···O═C H-bond but differing in their phenyl ring positions (a, g+, and g-). The fourth conformer forms a strained seven-membered hydrogen-bonded ring in which the amide groups lie in a nominally anti-parallel arrangement stacked on top of one another (labeled S7). This conformer is a close analogue of the amide-stacked conformer (S) found previously in γ2F, in which the Phe side chain is substituted at the γ2 position, Ac-γ2-Phe-NHMe (J. Am. Chem. Soc. 2009, 131, 14243-14245). IR population transfer spectroscopy was used to determine the fractional abundances of the γ4F conformers in the expansion. A combination of force field and density functional theory calculations is used to map out the conformational potential energy surfaces for γ4F and compare it with its γ2F counterpart. Based on this analysis, the phenyl ring prefers to take up structures that facilitate NH···π interactions in γ4F or avoid phenyl interactions with the C═O group in γ2F. The disconnectivity graph for γ4F reveals separate basins associated with the C9 and amide-stacked conformational families, which are separated by a barrier of about 42 kJ/mol. The overall shape of the potential energy surface bears a resemblance to peptides and proteins that have a misfolding pathway that competes with the formation of the native structure.

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The α/ß-peptide 11/9-helix and the ß-peptide 12/10-helix belong to "mixed" helices, in which two types of hydrogen bonds with opposite directionality alternate along the helical axis. cis-2-Aminocyclohexanecarboxylic acid (cis-ACHC) is known to promote these mixed helices and stabilize the helical propensity more than other acyclic ß-residues. Application of a mixed-helical backbone still requires sufficient solubility in aqueous solution. In this regard, we chose cis-4-aminopiperidine-3-carboxylic acid (cis-APiC) as a foldamer building block that can provide both sufficient aqueous solubility and mixed-helical propensity. Conformational analyses of α/ß- and ß-peptides containing a cis-APiC residue by circular dichroism spectroscopy and single-crystal X-ray crystallography suggest that the incorporation of cis-APiC instead of cis-ACHC can enhance the aqueous solubility of the mixed-helical peptides without any adverse effect on helical folding. In addition, the ratio between right- and left-handed 12/10-helices of ß-peptides can be rationalized by relative energies between the local conformations of the cis-APiC residue.

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A series of nylon-like oligomers was synthesized, which consisted of alternating cyclic 1,2-diamine and 1,2-dicarboxylic acid building blocks with a five-membered ring constraint. The nylon 2 4 oligomers are symmetric and display helical structures similar to the ß-peptide 12-helix with intramolecular 12-membered ring hydrogen bonds. The cyclopentane moiety allows each building block to promote 12-helical folding. In addition, a tartaric acid derivative with the acetonide moiety increases the solubility of oligomers in common organic solvents and promotes helical folding.

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OBJECTIVE: The purpose of this study is to examine the oncological safety of breast conserving surgery (BCS) for patients with multifocal breast cancer. SUMMARY BACKGROUND DATA: Few studies have reported about BCS for multifocal breast cancer. BCS for multifocal cancer has a risk of local failure in previous reports, whereas recent studies reported the feasibility of BCS. However, because all studies have dealt with a small number of patients, multifocal breast cancer is still considered a relative contraindication for BCS. METHODS: This retrospective study includes 478 patients with multifocal breast cancer who underwent BCS or mastectomy and 930 with unifocal cancer who underwent BCS for stage 0-II. Multifocal cancer was defined as 2 or more distinct cancers in the same quadrant. Of 478 patients, 147 underwent BCS and 331 underwent mastectomy. We compared the local recurrence rate (LRR), disease free survival, and overall survival for BCS with mastectomy for multifocal cancer. In addition, the LRR of BCS for multifocal cancer was compared for unifocal cancer. RESULTS: There is no significant difference in stage distribution and other clinical and pathologic characteristics except Her-2/neu for stage IIA between BCS and mastectomy for multifocal cancer. The mean follow-up period was 59.33 months (range, 1.00-177.20) for breast conserving group and 64.98 months (range, 6.23-196.03) for mastectomy group. The 5-year overall survival was 93.38% for BCS and 94.53% for mastectomy (log rank P = 0.208). The 5-year disease-free survival was 89.08% for BCS and 91.88% for mastectomy (log rank P = 0.451). The local failure occurred in 3 (2.0%) of 147 patient underwent BCS, 3 (0.9%) of 331 patients underwent mastectomy (P = 0.378). Compared with BCS for unifocal cancer patients, the LRR of patients with multifocal cancer was not statistically different (2.0% for multifocal, 1.3% for unifocal; P = 0.445). CONCLUSIONS: Our study demonstrates that BCS for multifocal breast cancer is oncologically safe in selected patients.

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