Cyclative Release Strategy to Obtain Pure Cyclic Peptides Directly from the Solid Phase.

The synthesis of large numbers of cyclic peptides─required, for example, in screens for drug development─is currently limited by the need of chromatographic purification of individual peptides. Herein, we have developed a strategy in which cyclic peptides are released from the solid phase in the pure form and do not need purification. Peptides with an N-terminal thiol group are synthesized on the solid phase via a C-terminal disulfide linker, their sidechain-protecting groups are removed while the peptides remain on the solid phase, and the peptides are finally released via a cyclative mechanism by the addition of a base that deprotonates the N-terminal thiol group and triggers an intramolecular disulfide-exchange reaction.

A Raf-like kinase is required for smoke-induced seed dormancy in .

Plants sense and integrate diverse stimuli to determine the timing for germination. A smoke compound, 3,4,5-trimethylfuran-2()-one (trimethylbutenolide, TMB), has been identified to inhibit the seed germination of higher plants. To understand the mode of action, we examined various physiological and molecular aspects of the TMB-dependent inhibition of seed germination in The results indicated that the effect of TMB is due to the enhanced physiological dormancy, which is modulated by other dormancy regulatory cues such as after-ripening, stratification, and ABA/GA signaling.

Targeted Degradation of Transcription Coactivator SRC-1 through the N-Degron Pathway.

Aberrantly elevated steroid receptor coactivator-1 (SRC-1) expression and activity are strongly correlated with cancer progression and metastasis. Here we report, for the first time, the development of a proteolysis targeting chimera (PROTAC) that is composed of a selective SRC-1 binder linked to a specific ligand for UBR box, a unique class of E3 ligases recognizing N-degrons. We showed that the bifunctional molecule efficiently and selectively induced the degradation of SRC-1 in cells through the N-degron pathway.

Synthesis and biological evaluation of potent benzoselenophene and heteroaromatic analogues of ()-1-(chloromethyl)-8-methoxy-2,3-dihydro-1-benzo[]indol-5-ol (-MCBI).

A diverse series of compounds (18a-x) were synthesized from ()-1-(chloromethyl)-8-methoxy-2,3-dihydro-1-benzo[]indol-5-ol (-MCBI) and benzoselenophene or heteroaromatic acids. These new compounds were evaluated for their cytotoxicity against the human gastric NCI-N87 and human ovarian SK-OV3 cancer cell lines. The incorporation of a methoxy substituent at the C-7 position of the -CBI unit enhances the cytotoxicity through its additional van der Waals interaction and gave a much higher potency than the corresponding -CBI-based analogues.

Oligomers of α-ABpeptoid/β -peptide hybrid.

Peptoids, oligomers of N-substituted glycines, have been attracting increasing interest due to their advantageous properties as peptidomimetics. However, due to the lack of chiral centers and amide hydrogen atoms, peptoids, in general, do not form folding structures except that they have α-chiral side chains. We have recently developed "peptoids with backbone chirality" as a new class of peptoid foldamers called α-ABpeptoids and demonstrated that they could have folding conformations owing to the methyl groups on chiral α-carbons in the backbone structure.

Solid-Phase Synthesis and Circular Dichroism Study of β-ABpeptoids.

The development of peptidomimetic foldamers that can form well-defined folded structures is highly desirable yet challenging. We previously reported on α-ABpeptoids, oligomers of -alkylated β²-homoalanines and found that due to the presence of chiral methyl groups at α-positions, α-ABpeptoids were shown to adopt folding conformations. Here, we report β-ABpeptoids having chiral methyl group at β-positions rather than α-positions as a different class of peptoids with backbone chirality.

Submonomer Strategy toward Divergent Solid-Phase Synthesis of α-ABpeptoids.

A novel submonomer solid-phase synthetic method for α-ABpeptoid oligomers is reported. Iterative submonomer coupling and Fukuyama-Mitsunobu alkylation enable facile, divergent synthesis of α-ABpeptoid oligomers substituted with chemically diverse side chains in excellent yields.

Solid-Phase Synthesis of Triostin A Using a Symmetrical Bis(diphenylmethyl) Linker System.

Triostin A is a symmetric bicyclic depsipeptide with very potent antitumoral activity because of its bisintercalation into DNA. In this study, we report a new synthetic strategy that exploits a structural symmetry of triostin A. First, we prepared a novel symmetric linker molecule that is labile under mildly acidic conditions and suitable for a solid-phase synthesis procedure.