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As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner. As demonstrated in the development of BMS-L1-RGD, which is an efficient programmed death-ligand 1 (PD-L1) degrader validated both

Hela cells or A549 cells stably expressing histone H2B-RFP were incubated with 10 μM of different PIPs for 24 h. Cells were then subjected to live-imaging using confocal microscopy. Scale bar, 10 μm.

(a) Hela cells or (b) A549 cells stably expressing histone H2B-RFP were incubated with 10 μM of PIP3. At different time points, cells were harvested, stained, and imaged. Scale bar, 50 μm. (c) Nuclear localization of PIP3 in A549 cells. Scale bar, 10 μm.

Live imaging of mitotic progression in PIP3 treated hTERT-RPE1 cells

(a and b) Plk1 mRNA levels (a) and Plk1 protein levels (b) in various cell lines. (c-e) Pearson correlation co-efficiency was calculated between Plk1 mRNA level, Plk1 protein expression level, and PIP3 sensitivity (represented by IC50 value).

(a and b) A549 cells were treated with different concentrations of PIP2 or PIP3. After 72 h of treatment, cells were incubated with 10 ng/ml TNF-α for additional 12 h, and then harvested for IL6 (a) and IL8 (b) qRT-PCR analysis.

(a) Comparison of the cellular uptake of PIP3 and Hoechst 33258. Hela cells were incubated with different concentrations of PIP3 or Hoechst 33258 for 24 hours. Fluorescent microscopy images were acquired and as shown. (b) PIP3 but not Hoechst 33258 shows Plk1 suppression ability. Hela cells were treated with different concentrations of PIP3 or Hoechst 33258 for 72 hours and then collected for western blotting analysis to examine the Plk1 expression. (c) Evaluation of PIP3 stability in vitro. Hela cells were treated with 10 μM PIP3 for 72 hours, then cells were collected and lysed. Released PIP3 was monitored by RP-HPLC analysis. PIP3 dissolved in water was served as control.

(a) Representative images of mice from vehicle group and PIP3-treated group on the sacrifice day. Yellow arrows indicate tumor locations. (b) Images of isolated tumors from vehicle group or PIP3-treated group. (c) In vivo cellular localization of PIP3. Frozen sections of tumors from PIP3-treated group were imaged under microscopy to visualize the cellular uptake of PIP3 in vivo. The nuclei were stained by Topro3. Scale bar, 100 μm.

(a and b) The hTERT-RPE1 cells and HUVEC cells were synchronized, PIP3 treated, and analyzed as in Figure 4a and 4b. Plk1 inhibition efficiency examined by western blotting was shown in the top. (c and d) Percentages of mitotic cells at different phases were quantified in these treated cells (n.s, not significant; n=3). (e) Time-lapse microscopy of nontransformed cells with or without PIP3 treatment. hTERT-RPE1 cells and HUVEC cells stably expressing histone H2B-RFP were treated with 0.1% DMSO or 20 μM of PIP3 for 72 h and analyzed by time-lapse imaging. (f and g) The duration of total mitosis (f) and time spent in each sub-stage of mitosis (g) were further quantified (n.s, not significant; n{greater than or equal to}25).

The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide–Hoechst conjugate, PIP3, targeted to specific DNA sequence in the PLK1 promoter. PIP3 could specifically inhibit the cell cycle–regulated Plk1 expression and consequently retard tumor cell growth. Cancer cells treated with PIP3 exhibited severe mitotic defects and increased apoptosis, whereas normal cells were not affected by PIP3 treatment. Furthermore, subcutaneous injection of PIP3 into mice bearing human cancer xenografts induced significant tumor growth suppression with low host toxicity. Therefore, PIP3 exhibits the potential as an effective agent for targeted cancer therapy. Mol Cancer Ther; 17(5); 988–1002. ©2018 AACR.

Hela cells were treated with or without 10 μM PIP3 for 72 hours and then labeled by Propidium iodide and Annexin V-FITC for detecting early and late apoptotic signal.

Divergent coupling reactions of imidazo[1,2-a]pyridines with N-methylanilines have been achieved in undivided cells under air and metal/oxidant-free oxidative electrochemical conditions.

A concise total synthesis of (±)-pileamartines A and B, a pair of alkaloids sharing an unprecedented tetracyclic skeleton, was achieved in 9 and 8 linear steps, respectively.

A microwave-promoted multicomponent reaction of 3-formylchromones, amines, and paraformaldehyde was achieved under catalyst-free and solvent-free conditions, delivering 5H-chromeno[2,3-d]pyrimidin-5-one derivatives in good to excellent yields via an unexpected annulation pathway, which further expanded the synthetic application of paraformaldehyde as a C1 building block.

Natural products are useful tools for biological mechanism research and drug discovery. Due to the excellent tumor cell growth inhibitory profile and sub-nanomolar potency, Coibamide A (CA), an N-methyl-stabilized depsipeptide isolated from marine cyanobacterium, has been considered as a promising lead compound for cancer treatment. However, the molecular anti-cancer mechanism of the action of CA remains unclear. Here, we showed that CA treatment induced caspase-independent cell death in breast cancer cells. CA treatment also led to severe lysosome defects, which was ascribed to the impaired glycosylation of lysosome membrane protein LAMP1 and LAMP2. As a consequence, the autophagosome-lysosome fusion was blocked upon CA treatment. In addition, we presented evidence that this autophagy defect partially contributed to the CA treatment-induced tumor cell death. Together, our work uncovers a novel mechanism underlying the anti-cancer action of CA, which will promote its further application for cancer therapy.

Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.

A microwave-promoted multicomponent reaction of 3-formylchromones, amines, and paraformaldehyde was achieved under catalyst-free and solvent-free conditions, delivering 5

We have developed a dearomatization-rearomatization strategy for the modification of peptides/proteins through a thiol-Michael addition to the electrophilic cyclohexadienone intermediate that is generated in situ via the oxidation of tyrosine. This strategy enriches the conjugation toolbox and has great potential for applications in medicinal chemistry and chemical biology.

Aurora kinase A (Aurora A) plays a critical role in regulating cell mitotic progression and has been considered as a promising drug target for cancer therapy. To develop a novel molecule targeting Aurora A with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide (PIP) Hoechst conjugate, PIP-Ht, targeting to a cell-cycle regulated DNA sequence locating at the promoter of human Aurora A gene (AURKA). PIP-Ht potently suppressed AURKA promoter activities, mRNA expression and protein level, induced tumor cell cycle delay and inhibited tumor cell proliferation in vitro. Furthermore, subcutaneous injection of PIP-Ht into mice bearing human cancer xenografts induced significant tumor growth suppression and cell apoptosis. Collectively, PIP-Ht exhibits the potential as an effective therapeutic candidate for the tumor treatment.

Azobenzene functionalized peptides are of great importance in photoresponsive biosystems and photopharmacology. Herein, we report an efficient approach to prepare azobenzene functionalized peptides through late-stage modification of tyrosine-containing peptides using a dearomatization-rearomatization strategy. This approach shows good chemoselectivity and site selectivity as well as sensitive group tolerance to various peptides. This method enriches the postsynthetic modification toolbox of peptides and has great potential to be applied in medicinal chemistry and chemical biology.

The global emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can only be solved with effective and widespread preventive and therapeutic strategies, and both are still insufficient. Here, we describe an ultrathin two-dimensional CuInP

Coibamide A (

Background Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder, and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD. Methods Forty-two consecutive SISMAD patients who were admitted to a single center between October 2009 and May 2018 were enrolled in this study. Based on their symptoms, 15 had conservative treatment, and 27 had endovascular treatment. The baseline characteristics, treatments, and follow-up results of the conservative group and endovascular group were analysed. Results The rates of symptom relief were 93.3% in the conservative group and 96.3% in the endovascular group. The procedure-related complications in the endovascular group included one case of pseudoaneurysm formation in the left brachial artery. During the follow-up period (median 28.5 months), a higher proportion of patients in the conservative group had symptom recurrence (42.9% in the conservative group versus 4.8% in the endovascular group, p p = 0.014) and a higher rate of superior mesenteric artery (SMA) remodeling (p Conclusions For symptomatic SISMAD, endovascularly treated patients had a lower rate of symptom recurrence and a higher rate of SMA remodeling in the long term. Prospective, multi-center studies are needed to confirm the long-term outcomes of both treatments.

There is no consensus for determining which vessel should be revascularized in patients with multiple diseased infrapopliteal arteries. The angiosome concept may guide a more efficient targeted direct revascularization. Therefore, we conducted a study to assess whether the regional evaluation of foot blood volume may guide direct revascularization (DR) and if it will lead to better perfusion improvement than indirect revascularization (IR). We performed a prospective single-center observational cohort study in patients treated in the Department of Vascular Surgery of Peking Union Medical College Hospital from November 2016 to April 2019. Twenty-seven patients treated with endovascular intervention were included. The intraoperative parenchymal blood volume of different foot regions was obtained for each patient using C-arm CT before and after intervention. The intervention procedure significantly increased the overall blood volume (48.95 versus 81.97 ml/1000 ml, p = 0.002). Patients with direct revascularization had a 197% blood volume increase while patients with indirect revascularization had a 39% increase (p = 0.028). The preoperative blood volume was higher in patients with mild symptoms than in patients with severe symptoms (58.20 versus 30.45 ml/1000 ml, p = 0.039). However, in regard to postoperative blood volume, no significant difference was discovered between these two groups (75.05 versus 95.01 ml/1000 ml, p = 0.275). Based on quantitative measurements, we conclude that overall blood volume can rise significantly after the intervention. Revascularizing the supplying vessel of the ischemic area directly will result in better perfusion improvement than restoring blood supply through the collateral circulation. Preoperative blood volume is associated with preoperative symptoms. • Flat panel detector CT can obtain intraoperative perfusion status and guide treatment in endovascular intervention. • Revascularizing the supplying vessel of the ischemic area directly will result in better perfusion improvement than restoring the blood supply through the collateral circulation. • Patients with severer clinical manifestations have lower blood volumes.

Objective The safety and effectiveness of using the hybrid approach to treat tandem carotid lesions is controversial, and the clinical significance of the technical variants on the perioperative outcomes has not been evaluated. The present meta-analysis was performed to evaluate the technique, safety, effectiveness, and long-term outcomes of the hybrid approach. Methods The PubMed, Embase, and Cochrane Library databases were searched to identify studies from January 1, 1996 to January 11, 2020. The baseline patient characteristics, comorbidities, procedural details, and perioperative and long-term outcomes were collected and analyzed. A pooled overall survival curve was drawn. Univariate analysis was performed to compare the perioperative stroke risk between subgroups. Results Overall, 275 patients (mean age, 66.94 years) from 15 studies were included. All the patients had presented with tandem stenosis of ≥50%, and 67.2% were symptomatic. The overall technical success rate was 99.8% (95% confidence interval [CI], 98.0%-100.0%). The pooled perioperative complications rates were as follows: death, 1.5% (95% CI, 0.0%-2.9%); stroke, 2.6% (95% CI, 0.7%-4.4%); combined stroke/death, 3.3% (95% CI, 1.2%-5.4%); and myocardial infarction, 3.2% (95% CI, 0.7%-9.1%). The overall primary patency rates were 99.2% (95% CI, 96.0%-100.0%) and 88.2% (95% CI, 78.8%-95.4%) at 1 and 2 years, respectively. Reintervention was performed in 6.6% of the patients (95% CI, 3.0%-11.2%). The pooled overall survival rates were 89.9% (95% CI, 83.7%-96.7%), 83.7% (95% CI, 75.9%-92.2%), and 75.9% (95% CI, 66.5%-86.7%) at 1, 3, and 5 years, respectively. Operations in which carotid endarterectomy was performed first carried a significantly greater risk of perioperative stroke compared with those in which proximal intervention had been performed first (5.7% vs 0.0%; P = .01). No difference was found in perioperative stroke risk between the subgroups of baseline symptomatic status (asymptomatic, 5.1%; symptomatic, 1.9%; P = .32), preoperative antiplatelet therapy (dual, 3.6%; single, 5.8%; P = .79), and carotid clamping during intervention (clamping, 2.8%; unclamping, 6.3%; P = .40). Conclusions For patients with a presumed high risk of neurologic events because of carotid tandem lesions, the hybrid approach could be considered a reasonable option with high technical success and acceptable perioperative and long-term results. Performing carotid artery stenting before carotid endarterectomy and administering perioperative dual antiplatelet therapy should be considered to promote technical success and better outcomes. Prospective and randomized controlled studies are needed to confirm the results and provide recommendations on patient selection for the hybrid approach.

Hairpin pyrrole-imidazole (Py-Im) polyamides are a class of programmable minor-groove binders that recognize pre-determined DNA double helixes with high affinity and specificity. They are capable of regulating gene expression by modulating the activity of transcription factors. To date, Py-Im polyamides have been successfully applied as a potent tool to disturb DNA functions and considered as a group of promising candidates for the clinical applications. Herein, this review will focus on summarizing the recent advances of Py-Im polyamides from their synthesis to applications via various modifications at the molecular level.

The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide–Hoechst conjugate, PIP3, targeted to specific DNA sequence in the PLK1 promoter. PIP3 could specifically inhibit the cell cycle–regulated Plk1 expression and consequently retard tumor cell growth. Cancer cells treated with PIP3 exhibited severe mitotic defects and increased apoptosis, whereas normal cells were not affected by PIP3 treatment. Furthermore, subcutaneous injection of PIP3 into mice bearing human cancer xenografts induced significant tumor growth suppression with low host toxicity. Therefore, PIP3 exhibits the potential as an effective agent for targeted cancer therapy. Mol Cancer Ther; 17(5); 988–1002. ©2018 AACR.

No abstract available.

Background: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD. Methods: Forty-two consecutive SISMAD patients between October 2009 and May 2018 in a single center were enrolled in the study. Based on their symptoms, 15 had conservative treatment and 27 had endovascular treatment. The baseline characteristics, treatments, and follow-up results of the conservative group and endovascular group were analyzed. Results: The rate of symptom relief was 93.3% in the conservative group and 96.3% in the endovascular group, respectively. The procedure-related complications in the endovascular group included one case of pseudoaneurysm formation in the left brachial artery. During the follow-up period (median 28.5 months), a higher proportion of patients in the conservative group had symptom recurrence (42.9% in the conservative group versus 4.8% in the endovascular group, p < 0.001). Four patients in the conservative group and one patient in the endovascular group had additional endovascular intervention during follow-up. Compared with the conservative group, patients in the endovascular group had statistically significantly longer symptom-free survival ( p = 0.014) and a higher rate of superior mesenteric artery (SMA) remodeling ( p < 0.001). Conclusions: For symptomatic SISMAD, endovascularly treated patients had a lower rate of symptom recurrence and a higher rate of SMA remodeling in the long term. Endovascular treatment should be considered as the first-line treatment of SISMAD.

Background The performance of drug-coated balloons (DCBs) in femoropopliteal interventions has been proven through randomized trials in short lesions and lesions with relatively low proportion of occlusions. There is limited evidence of DCBs in long or occlusive lesions. This study is to investigate the efficacy of the paclitaxel-coated balloon for treatment of long and occlusive femoropopliteal arterial lesions. Methods A single-arm trial including 44 femoropopliteal lesions (chronic total occlusion (CTO) plus > 10 cm) treated with DCBs was performed to collect data of average 1-year follow-up. Endpoints contain primary patency, target lesion revascularization (TLR), amelioration of the Rutherford classification, change of ankle brachial index (ABI) and major adverse events. Results Technical success is 97.7% while device success is 100%. Mean lesion length was 186 ± 86.3 cm. Stent implantation was performed in 13.6%. Cumulative probability of primary patency was 78.8% ± 6.8% at 1 year while that of freedom from TLR was 91.4% ± 4.9%. Rutherford classification improved from average 3.3 ± 1.0 to 2.1 ± 1.4 (p p = 0.002). No major adverse event was observed. Conclusion These results suggest that it is safe and effective to treat long and totally occlusive femoropopliteal artery disease with DCBs. Further studies are demanded to confirm these results.

Although nanomaterials have shown promising biomedical application potential, incomplete understanding of their molecular interactions with biological systems prevents their inclusion into mainstream clinical applications. Here we show that black phosphorus (BP) nanomaterials directly affect the cell cycle's centrosome machinery. BP destabilizes mitotic centrosomes by attenuating the cohesion of pericentriolar material and consequently leads to centrosome fragmentation within mitosis. As a result, BP-treated cells exhibit multipolar spindles and mitotic delay, and ultimately undergo apoptosis. Mechanistically, BP compromises centrosome integrity by deactivating the centrosome kinase polo-like kinase 1 (PLK1). BP directly binds to PLK1, inducing its aggregation, decreasing its cytosolic mobility and eventually restricting its recruitment to centrosomes for activation. With this mechanism, BP nanomaterials show great anticancer potential in tumour xenografted mice. Together, our study reveals a molecular mechanism for the tumoricidal properties of BP and proposes a direction for biomedical application of nanomaterials by exploring their intrinsic bioactivities.

Background: Infrarenal aortic occlusion (IAO) is a complete occlusion of infrarenal aorta, which is the most complicated and severe subclass of aortoiliac occlusive disease (AIOD). The first-line treatment for IAO is bypass surgery due to its favorable patency rate. As endovascular technique advances, several retrospective studies have reported their endovascular experience for IAO. However, whether endovascular treatment(EVT) is comparable to bypass surgery for IAO required further study. This research was to study the safety and efficacy of EVT for IAO compared to bypass surgery. Methods: From 2003 to 2017, 44 consecutive patients with IAO was treated with EVT(n=16) or aortofemoral bypass surgery(n=28). The therapeutic strategy depended on patient’s will and state of health. Demographics, comorbidity, mortality, complication rate, and symptom-free survival proportion was compared by T-tests or chi-square test, to illustrate the safety and efficacy of EVT and bypass surgery. Results:The demographics and pre-operative Rutherford classification equally distributed in the two groups(P>0.05). As for technical success, comorbidities, mortality, complication rate, and Rutherford classification after procedures, clinical success, no significant difference was observed(P>0.05). The median post-procedure hospital stay was 4 days in the EVT group and was significantly shorter than that of the bypass, which was 11 days(P

Tyrosine kinase inhibitor (TKI) therapy is the standard treatment for chronic phase (CP)-chronic myeloid leukemia (CML), yet patients in blast crisis (BC) phase of CML are unlikely to respond to TKI therapy. The transcription factor E2F1 is a down-stream target of the tyrosine kinase BCR-ABL1 and is up-regulated in TKI-resistant leukemia stem cells (LSC). Pyrrole imidazole polyamides (PA) are minor groove binders which can be programmed to target DNA sequences in a gene-selective manner. This manuscript describes such an approach with a PA designed to down-regulate E2F1 controlled gene expression by targeting a DNA sequence within 100 base pairs (bp) upstream of the E2F1 consensus sequence. Human BC-CML KCL22 cells were assessed after treatment with PA, TKI or their combination. Our PA inhibited BC-CML cell expansion based on cell density analysis compared to an untreated control after a 48-hour time-course of PA treatment. However, no evidence of cell cycle arrest was observed among BC-CML cells treated with PA, with respect to their no drug control counterparts. Thus, this work demonstrates that PAs are effective in inhibiting E2F1 TF activity which results in a temporal reduction in BC-CML cell number. We envisage that PAs could be used in the future to map genes under E2F1 control in CML LSCs.

// Jianchao Zhang 1 , Ximing Shao 1 , Haiyan Sun 1 , Ke Liu 1 , Zhihao Ding 1 , Juntao Chen 1 , Lijing Fang 1 , Wu Su 1 , Yang Hong 4 , Huashun Li 2, 3 , Hongchang Li 1 1 Shenzhen Key Laboratory for Molecular Biology of Neural Development, Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China 2 SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine and Advanced Institute of Translational Medicine, Shanghai 200123, China 3 ATCG Corporation, BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China 4 Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA Correspondence to: Hongchang Li, email: hc.li@siat.ac.cn Huashun Li, email: huashunli@tongji.edu.cn Keywords: NUMB, EMT, TNBC, Notch, metastasis Received: March 26, 2016 Accepted: July 19, 2016 Published: August 05, 2016 ABSTRACT Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with higher rates of early relapse and metastasis, is frequently associated with aberrant activation of epithelial-mesenchymal transition (EMT). Nonetheless, how EMT is initiated and regulated during TNBC progression is not well understood. Here, we report that NUMB is a negative regulator of EMT in both human mammary epithelial cells and breast cancer cells. Reduced NUMB expression was significantly associated with elevated EMT in TNBC. Conversely, overexpression of NUMB strongly attenuated the EMT program and metastasis of TNBC cell lines. Interestingly, we showed that NUMB employs different molecular mechanisms to regulate EMT. In normal mammary epithelial cells and breast cancer cells expressing wild-type p53, NUMB suppressed EMT by stabilizing p53. However, in TNBC cells, loss of NUMB facilitated the EMT program by activating Notch signaling. Consistent with these findings, low NUMB expression and high Notch activity were significantly correlated with the TNBC subtype in patients. Collectively, these findings reveal novel molecular mechanisms of NUMB in the regulation of breast tumor EMT, especially in TNBC.

The effectiveness of computational tools in determining relative configurations of complex molecules is investigated, using natural products mandelalides A-D and coibamide A, towards a generalized recipe for the scientific community at large. Ultimately, continuing efforts in this vein will accelerate and strengthen relative structure elucidation of complex molecules, such as natural products. Molecular mechanics conformational search, quantum mechanical NMR chemical shift predictions, and DP4 analyses led to confirmation of the revised structures of mandelalides A-D and coibamide A. All chiral centers in the northern hemisphere of mandelalides A-D are inverted with respect to the originally proposed structures, in agreement with recent total syntheses of mandelalide A by Ye, Furstner & Carter. In the case of coibamide A, it was found that Fang & Su's revision, in which both the macrocycle [MeAla(11)] and the side chain [HIV(2)] residues are inverted from l to d, was consistent with the authentic natural product and computations.