1. Volume 22, Issue 12, Pages 1653-1661 (December 2015)
Synthetic Peptides as cGMP-Independent Activators of cGMP-Dependent Protein Kinase Iα 
Thomas M. Moon, Nathan R. Tykocki, Jessica L. Sheehe, Brent W. Osborne, Werner Tegge, Joseph E. Brayden, Wolfgang R. Dostmann 
Chemistry & Biology 
Volume 22, Issue 12, Pages (December 2015)
DOI: /j.chembiol
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2. Chemistry & Biology 2015 22, 1653-1661DOI: (10. 1016/j. chembiol. 2015
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3. Figure 1
Structure of the cGMP Binding Sites from the Regulatory Domain of PKG Iα
(A) Emphasis is given to the asymmetric interaction of helical segments between the cGMP binding sites (denoted B and B′) on opposing protomers of PKG Iα (PDB: 3SHR). Also shown are the switch helix domains (SW and SW′) from each protomer.
(B) Directional view, indicated by arrow in (A), detailing the interaction of the knob residues (F350′, F351′, L354′) with the nest (N353′; not depicted).
(C) Electrostatic surface representation of the cGMP B-site demonstrating its amino acid composition, the boundaries of the nest, and its location relative to the cGMP- binding site. The dashed line represents the demarcation of the regions of the nest and the cGMP-binding site within the B domain.
Chemistry & Biology  , DOI: ( /j.chembiol )
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4. Figure 2 Activation of PKG Iα by S-Tides
(A and B) Activity of PKG Iα was measured using peptides with (A) C-terminal truncation modifications and (B) N-terminal truncation mutants derived from the parent compound S1.1. Activity is expressed as a percentage relative to 5 μM cGMP for individual experiments. Values indicated are the mean ± SD.
(C and D) Secondary structure determination of (C) C-terminal and (D) N-terminal truncation mutants as measured by CD spectroscopy. Mean residue ellipticity (θ) is expressed as mdeg × cm2/dmol × residue.
Chemistry & Biology  , DOI: ( /j.chembiol )
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5. Figure 3
Effects of Peptide- or cGMP-Treated PKG Iα Added to the Cytosolic Face of Excised, Inside-Out Membrane Patches Containing KCa1.1 Channels
(A) Representative control (left) and experimental traces (right) of single KCa1.1 channel openings in excised membrane patches from cerebral artery myocytes.
(B) The combined results of single KCa1.1 recordings demonstrate a substantially increased NPo versus control for saturating cGMP levels and S-tides S1.1 and S1.5 (†p < 0.002, ∗p < 0.05). Mean values with SEM are represented. Dashed line indicates normalized channel activity from control patches.
Chemistry & Biology  , DOI: ( /j.chembiol )
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6. Figure 4 Intracellular Delivery of S-Tides by Reverse Permeablization
Posterior cerebral arteries were subjected to reverse permeabilization with FITC-βAla2-S1.5 (experimental, left panel) and S1.5 (control, right panel) peptides. Following digestion using papain and collagenase, single smooth muscle cells were imaged using differential interference contrast microscopy (DIC) and confocal fluorescence microscopy.
Chemistry & Biology  , DOI: ( /j.chembiol )
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7. Figure 5
S-Tides Cause BK Channel-Dependent Inhibition of Myogenic Tone Development in Posterior Cerebral Arteries
(A) Diameter measurements for endothelium-denuded, reversibly permeabilized arteries demonstrating myogenic tone response in (Aa) control and (Ab) S1.5-treated arteries. (Ac–Ae) Summarized results of diameter measurements for endothelium-denuded arteries in control and permeabilized treatments are shown with values represented as the mean ± SEM. Differences in myogenic tone in response to pressure (Ac) as well as paxilline-induced constriction (Ad) are shown (∗p < 0.05).
(B) Diameter measurements from endothelium-intact arteries for controls (Ba) and S1.5-treated arteries (Bb) show unaltered myogenic tone response (Bc) but small differences in paxilline-induced constriction of control and S1.5-treated arteries (Bd, ∗p < 0.02). For both sets of experiments, total constriction (Ae, Be) was unchanged between controls and S1.5-treated arteries.
Chemistry & Biology  , DOI: ( /j.chembiol )
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