Development and pharmacological characterization of novel multi- calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide receptor antagonists.

Objective: This study aimed to provide proof-of-concept that multi-receptor antagonist peptides can be generated by covalently linking independent antagonist peptides that block calcitonin gene-related peptide (CGRP) or pituitary adenylate cyclase-activating peptide (PACAP)/vasoactive intestinal peptide (VIP) (PACAP) activity.

Background: The neuropeptides CGRP and PACAP are implicated in migraine and pain pathogenesis. CGRP and PACAP are elevated during a migraine attack, and following infusion of either peptide, patients develop migraine-like attacks.

Deconstruction of a Memory Engram Reveals Distinct Ensembles Recruited at Learning.

How are associative memories formed? Which cells represent a memory, and when are they engaged? By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we identified non-overlapping dorsal CA1 neuronal ensembles that are differentially active during associative fear memory acquisition. We dissected the acquisition experience into periods during which salient stimuli were presented or certain mouse behaviors occurred and found that cells associated with specific acquisition periods are sufficient alone to drive memory expression and contribute to fear engram formation. This study delineated the different identities of the cell ensembles active during learning, and revealed, for the first time, which ones form the core engram and are essential for memory formation and recall.

Deconstruction of a memory engram reveals distinct ensembles recruited at learning.

How are associative memories formed? Which cells represent a memory, and when are they engaged? By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we identified non-overlapping dorsal CA1 neuronal ensembles that are differentially active during associative fear memory acquisition. We dissected the acquisition experience into periods during which salient stimuli were presented or certain mouse behaviors occurred and found that cells associated with specific acquisition periods are sufficient alone to drive memory expression and contribute to fear engram formation. This study delineated the different identities of the cell ensembles active during learning, and revealed, for the first time, which ones form the core engram and are essential for memory formation and recall.

A Stable Dehydratase Complex Catalyzes the Formation of Dehydrated Amino Acids in a Class V Lanthipeptide.

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides that bear the characteristic lanthionine (Lan) or methyllanthionine (MeLan) thioether linkages. (Me)Lan moieties bestow lanthipeptides with robust stability and diverse antimicrobial, anticancer, and antiallodynic activities. Installation of (Me)Lan requires dehydration of serine and threonine residues to 2,3-dehydroalanine (Dha) and ()-2,3-dehydrobutyrine (Dhb), respectively.

Total Synthesis of (-)-Cordycicadin D and 3,4-trans-Cordycicadins A and B: Entry to the 3,4-trans-Fused Cordycicadin Framework.

Cordycicadins A-D are four C polyketides, all containing a γ-lactone fused to a 10-membered lactone. The proposed biosynthetic pathway for the cordycicadins anticipates the formation of two more natural products which are unknown. We report the total synthesis of (-)-cordycicadin D and the two anticipated natural products 3,4-trans-cordycicadins A and B.